This study investigated the protective effects of curcumin against lead-induced oxidative stress and brain damage in pregnant rats and their fetuses. Pregnant rats were exposed to two doses of lead acetate, with or without curcumin supplementation. Lead exposure resulted in toxicity for both mothers and fetuses, as well as increased oxidative stress and brain histopathology. Co-treatment with curcumin significantly reduced lead levels and oxidative stress, and improved brain histopathology. The results suggest that curcumin has an ameliorative effect against lead-induced neurotoxicity by reducing oxidative stress and reversing tissue damage.
Increase your Understanding of the Pathogenesis of Gluten Spectrum DisordersCell Science Systems
Recently, researchers at Harvard University, Alessio Fasano et. al., and the National Institutes of Health (laboratories of immunology and cellular and molecular biology), reported real-time microscopic observations of gluten-induced neutrophil activation.
According to authors, " To what extent neutrophil function adds to, or protects against, gluten intolerance is currently under vigorous investigation."
This presentation will shed light on this question. It will also review the Fasano study and examine the role of neutrophil function in multiple disease conditions, as well as explore how neutrophil function may also play a dual role in protecting the body from the untoward effects of dietary and environmental agents.
International Journal of Engineering and Science Invention (IJESI)inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Increase your Understanding of the Pathogenesis of Gluten Spectrum DisordersCell Science Systems
Recently, researchers at Harvard University, Alessio Fasano et. al., and the National Institutes of Health (laboratories of immunology and cellular and molecular biology), reported real-time microscopic observations of gluten-induced neutrophil activation.
According to authors, " To what extent neutrophil function adds to, or protects against, gluten intolerance is currently under vigorous investigation."
This presentation will shed light on this question. It will also review the Fasano study and examine the role of neutrophil function in multiple disease conditions, as well as explore how neutrophil function may also play a dual role in protecting the body from the untoward effects of dietary and environmental agents.
International Journal of Engineering and Science Invention (IJESI)inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
"Insulin Independence" Summit on Capitol HillDavid Edelman
These slides are from the April 24, 2013 "Insulin Independence" summit at the Canon House Office Building on Capitol Hill in Washington, DC. The event previewed the future of combination therapies to restore insulin production to people living with type 1 diabetes.
Something remarkable happens when some women with type 1 diabetes become pregnant: they start producing completely normal levels of insulin.
You read that correctly: one third of pregnant women, including those who’ve had it for 20 years or more, have reduced insulin needs during pregnancy. Some need no injected insulin at all. This knowledge may soon help everyone living with type 1 diabetes. How is this possible?
Two special things happen during pregnancy. First, the body relaxes the immune system to prevent it from harming the fetus. Second, it floods the body with hormones that promote growth. This causes something that researchers long thought was impossible: brand new islet cells start forming and producing insulin.
The combination therapy approach looks to mimic this effect and transform the treatment of diabetes.
BOOSTING YOUR IMMUNITY During the COVID 19 PandemicLouis Cady, MD
In this presentation, presented as a live webinar on Monday, April 27th, Dr. Louis Cady of the Cady Wellness Institute reviewed practical, common-sense things that can be done to boost your immunity, with documentation from the peer-reviewed medical literature. Dr. Cady also reviews supplements and nutrients that are established in the peer-reviewed medical literature as having antiviral capabilities. These include Vitamins C,D, and E, Zinc, carotenoids and antioxidants, probiotics, the reishi mushroom, elderberry, cannabidiol (CBD - not marijuana or weed!).
Points presented are scrupulously documented from the medical literature. This presentation does not guarantee or represent that using ANY of these nutrients will "keep you from getting infected or dying" from COVID 19. They are presented for your thoughtful consideration.
Is IL1R1 required for celastrol’s leptin-sensitization and antiobesity effects?LucyPi1
The article by Xudong Feng et al. [1], published on 4 March 2019 in the journal of Nature Medicine, showed the relationship between natural product celastrol and obesity. The researchers demonstrated celastrol was able to sensitize leptin and displayed antiobesity effects through IL1R1 (Interleukin-1 receptor 1). It was proved that IL1R1 was a gatekeeper for celastrol’s metabolic actions.
Recent research suggests that a variety of lifestyle - especially dietary - changes influencing the integrity of gastrointestinal function may be driving at least some portion of the increased prevalence of illnesses of civilization, including neuropsychiatric problems, such as autism, attention-deficit-hyperactivity disorder, major depression, obsessive-compulsive disorder and Alzheimer disease. One area of interest involves the relationship between the gut's microbiome (as well as the related functional integrity of the gastrointestinal tract) and mental health.
Diabetes mellitus is spreading around the world, penetrating populations not only in poor and developing countries, but also in developed ones. Propolis, a complex resinous material collected by honey bees from buds and exudates of certain plant sources, containing flavonoids pinocebrin, galangin, chrysin, and caffeic acid phenethyl ester.
The use of propolis as an alternative healing therapy for type-2 diabetes mellitus has been claimed to alleviate the disease. Previous studies state that propolis improves normal homeostasis by balancing the body’s condition through the enhancement of the immune system. The histological analysis of the liver shows that at a dose of 50–200 mg/kg BW propolis does not show a toxic effect so that the dose is categorized safe.
Therefore, the ethanolic soluble derivative of propolis (EEP) extract warrant further studies as an antidiabetic agent that is safe for humans.
European Commission Joint Research Center presents chemical screening methodology for the impact assessment on criteria to identify endocrine disruptors
A technical meeting on the JRC methodology for evidence screening of chemicals developed in the context of the Impact Assessment on criteria to identify Endocrine Disruptors took place on 6 November 2015 in Brussels.
The aim of this technical meeting was to present to Member States, Members of the European Parliament, countries from outside the EU and stakeholders the methodology developed by the JRC to estimate which chemicals may fall under the different options for criteria to identify endocrine disruptors as outlined in the roadmap. This methodology was developed in the framework of the impact assessment carried out by the European Commission on criteria to identify endocrine disruptors, in the context of the Plant Protection Products Regulation (EC) 1107/2009 and the Biocidal Products Regulation (EU) 528/2012.
Sources
* Methodology for EU EDC screening http://ec.europa.eu/health/endocrine_disruptors/docs/ev_20151106_co01_en.pdf
* Selection of chemical substances to be screened in the context of the impact assessment on criteria to identify endocrine disruptors http://ec.europa.eu/health/endocrine_disruptors/docs/impactassessment_chemicalsubstancesselection_en.pdf
Thymoquinone ameliorates oxidative damage and histopathological changes of de...Prof. Hesham N. Mustafa
ABSTRACT
Lead (Pb) toxicity is known to be a chief environmental health issue, especially for pregnant
women and young children. Today, the use of medicinal herbs in the treatment of many diseases
and different toxic agents has become highly accepted due to their effectiveness and lower costs.
Thymoquinone (TQ), which is extracted from Nigella sativa seeds, is a potent antioxidant and anti
inflammatory agent. This study was designed to explore the optional protectivity of TQ against
maternal and fetal oxidative stress and brain damage induced by Pb administration. Pregnant
rats were distributed into seven groups: control group, TQ group, DMSO group, two groups Pb
treated (160 and 320 ppm), and two groups Pb-treated (160 and 320 ppm) co-treated with TQ.
Administration started from gestation day 1 (GD1) to day 20 (GD20) through oral gavage once
daily. Lead administration caused a dose-dependent toxicity for both mothers and fetuses. Also,
the histopathological assessment of the brains from Pb-treated groups showed marked altera
tions. Co-treatment of with TQ and Pb caused a significant decrease in Pb levels as compared
with those treated with Pb alone and amelioration of histopathological changes in the brains. It
was concluded that co-treatment of TQ along with gestational Pb exposure could mitigate the
effects against Pb-induced maternal and fetal neurotoxicity.
KEYWORDS
Lead; oxidative stress; brain;
Thymoquinone; fetal toxicity
Protective effect of garlic extract against maternal and fetal cerebellar dam...Prof. Hesham N. Mustafa
Background: In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy.
Materials and methods: Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination.
Results: The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes.
Conclusions: This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).
Keywords: Purkinje cells; garlic; glial fibrillary acidic protein; lead.
In this study, we focused on the effect of β-glucan supplementation of children with chronic respiratory problems. We measured the levels of cortisol, salivary IgE and cotinine in 56 children and evaluated the effect of 30 day supplementation with 100 mg/day oral dose of yeast-derived β-glucan. Our results showed strong decrease of cotinine and cortisol levels in saliva of β-glucan-supplemented children. The increase of total salivary IgE levels in both groups was not statistically significant. The positive effects of complex curative treatment using β-glucan were accompanied by increased physical endurance and by significant reduction of negative clinical problems of affected children.
Zingiber Officinale Alleviates Maternal and Fetal Hepatorenal Toxicity Induce...Prof. Hesham N. Mustafa
This study was designed to address the protective effects of Zingiber officinale on the toxic outcomes of prenatal Cadmium administration on pregnancy outcome. Pregnant female Sprague-Dawley rats were randomly divided into four groups (eight rats/each), control group received distilled water, 2nd group treated with 8.8 mg of CdCl2/kg b. wt, 3rd group treated with 250 mg of Zingiber officinale/kg b. wt, and 4th group treated with 250 mg of Zingiber officinale/kg b. wt, followed by 8.8 mg of CdCl2/kg b.wt. Daily body weight of pregnant was recorded from GD1-GD20, and then pregnant rats were sacrificed at GD20. Samples of maternal and fetal livers and kidneys were processed for histological examination. Administration of Cd to pregnant rats showed adverse effects on pregnant mothers and their fetuses; reduced maternal weight gain, reduced absolute organ weights, reduced fetal growth parameters and placental weights together with altered histological appearance of the maternal and fetal livers and kidneys. While co-administration of Zingiber officinale showed an improvement of these toxic alterations. Zingiber officinale through its antioxidant activity could be beneficial against toxic outcomes of Cd exposure during pregnancy.
"Insulin Independence" Summit on Capitol HillDavid Edelman
These slides are from the April 24, 2013 "Insulin Independence" summit at the Canon House Office Building on Capitol Hill in Washington, DC. The event previewed the future of combination therapies to restore insulin production to people living with type 1 diabetes.
Something remarkable happens when some women with type 1 diabetes become pregnant: they start producing completely normal levels of insulin.
You read that correctly: one third of pregnant women, including those who’ve had it for 20 years or more, have reduced insulin needs during pregnancy. Some need no injected insulin at all. This knowledge may soon help everyone living with type 1 diabetes. How is this possible?
Two special things happen during pregnancy. First, the body relaxes the immune system to prevent it from harming the fetus. Second, it floods the body with hormones that promote growth. This causes something that researchers long thought was impossible: brand new islet cells start forming and producing insulin.
The combination therapy approach looks to mimic this effect and transform the treatment of diabetes.
BOOSTING YOUR IMMUNITY During the COVID 19 PandemicLouis Cady, MD
In this presentation, presented as a live webinar on Monday, April 27th, Dr. Louis Cady of the Cady Wellness Institute reviewed practical, common-sense things that can be done to boost your immunity, with documentation from the peer-reviewed medical literature. Dr. Cady also reviews supplements and nutrients that are established in the peer-reviewed medical literature as having antiviral capabilities. These include Vitamins C,D, and E, Zinc, carotenoids and antioxidants, probiotics, the reishi mushroom, elderberry, cannabidiol (CBD - not marijuana or weed!).
Points presented are scrupulously documented from the medical literature. This presentation does not guarantee or represent that using ANY of these nutrients will "keep you from getting infected or dying" from COVID 19. They are presented for your thoughtful consideration.
Is IL1R1 required for celastrol’s leptin-sensitization and antiobesity effects?LucyPi1
The article by Xudong Feng et al. [1], published on 4 March 2019 in the journal of Nature Medicine, showed the relationship between natural product celastrol and obesity. The researchers demonstrated celastrol was able to sensitize leptin and displayed antiobesity effects through IL1R1 (Interleukin-1 receptor 1). It was proved that IL1R1 was a gatekeeper for celastrol’s metabolic actions.
Recent research suggests that a variety of lifestyle - especially dietary - changes influencing the integrity of gastrointestinal function may be driving at least some portion of the increased prevalence of illnesses of civilization, including neuropsychiatric problems, such as autism, attention-deficit-hyperactivity disorder, major depression, obsessive-compulsive disorder and Alzheimer disease. One area of interest involves the relationship between the gut's microbiome (as well as the related functional integrity of the gastrointestinal tract) and mental health.
Diabetes mellitus is spreading around the world, penetrating populations not only in poor and developing countries, but also in developed ones. Propolis, a complex resinous material collected by honey bees from buds and exudates of certain plant sources, containing flavonoids pinocebrin, galangin, chrysin, and caffeic acid phenethyl ester.
The use of propolis as an alternative healing therapy for type-2 diabetes mellitus has been claimed to alleviate the disease. Previous studies state that propolis improves normal homeostasis by balancing the body’s condition through the enhancement of the immune system. The histological analysis of the liver shows that at a dose of 50–200 mg/kg BW propolis does not show a toxic effect so that the dose is categorized safe.
Therefore, the ethanolic soluble derivative of propolis (EEP) extract warrant further studies as an antidiabetic agent that is safe for humans.
European Commission Joint Research Center presents chemical screening methodology for the impact assessment on criteria to identify endocrine disruptors
A technical meeting on the JRC methodology for evidence screening of chemicals developed in the context of the Impact Assessment on criteria to identify Endocrine Disruptors took place on 6 November 2015 in Brussels.
The aim of this technical meeting was to present to Member States, Members of the European Parliament, countries from outside the EU and stakeholders the methodology developed by the JRC to estimate which chemicals may fall under the different options for criteria to identify endocrine disruptors as outlined in the roadmap. This methodology was developed in the framework of the impact assessment carried out by the European Commission on criteria to identify endocrine disruptors, in the context of the Plant Protection Products Regulation (EC) 1107/2009 and the Biocidal Products Regulation (EU) 528/2012.
Sources
* Methodology for EU EDC screening http://ec.europa.eu/health/endocrine_disruptors/docs/ev_20151106_co01_en.pdf
* Selection of chemical substances to be screened in the context of the impact assessment on criteria to identify endocrine disruptors http://ec.europa.eu/health/endocrine_disruptors/docs/impactassessment_chemicalsubstancesselection_en.pdf
Thymoquinone ameliorates oxidative damage and histopathological changes of de...Prof. Hesham N. Mustafa
ABSTRACT
Lead (Pb) toxicity is known to be a chief environmental health issue, especially for pregnant
women and young children. Today, the use of medicinal herbs in the treatment of many diseases
and different toxic agents has become highly accepted due to their effectiveness and lower costs.
Thymoquinone (TQ), which is extracted from Nigella sativa seeds, is a potent antioxidant and anti
inflammatory agent. This study was designed to explore the optional protectivity of TQ against
maternal and fetal oxidative stress and brain damage induced by Pb administration. Pregnant
rats were distributed into seven groups: control group, TQ group, DMSO group, two groups Pb
treated (160 and 320 ppm), and two groups Pb-treated (160 and 320 ppm) co-treated with TQ.
Administration started from gestation day 1 (GD1) to day 20 (GD20) through oral gavage once
daily. Lead administration caused a dose-dependent toxicity for both mothers and fetuses. Also,
the histopathological assessment of the brains from Pb-treated groups showed marked altera
tions. Co-treatment of with TQ and Pb caused a significant decrease in Pb levels as compared
with those treated with Pb alone and amelioration of histopathological changes in the brains. It
was concluded that co-treatment of TQ along with gestational Pb exposure could mitigate the
effects against Pb-induced maternal and fetal neurotoxicity.
KEYWORDS
Lead; oxidative stress; brain;
Thymoquinone; fetal toxicity
Protective effect of garlic extract against maternal and fetal cerebellar dam...Prof. Hesham N. Mustafa
Background: In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy.
Materials and methods: Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination.
Results: The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes.
Conclusions: This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).
Keywords: Purkinje cells; garlic; glial fibrillary acidic protein; lead.
In this study, we focused on the effect of β-glucan supplementation of children with chronic respiratory problems. We measured the levels of cortisol, salivary IgE and cotinine in 56 children and evaluated the effect of 30 day supplementation with 100 mg/day oral dose of yeast-derived β-glucan. Our results showed strong decrease of cotinine and cortisol levels in saliva of β-glucan-supplemented children. The increase of total salivary IgE levels in both groups was not statistically significant. The positive effects of complex curative treatment using β-glucan were accompanied by increased physical endurance and by significant reduction of negative clinical problems of affected children.
Zingiber Officinale Alleviates Maternal and Fetal Hepatorenal Toxicity Induce...Prof. Hesham N. Mustafa
This study was designed to address the protective effects of Zingiber officinale on the toxic outcomes of prenatal Cadmium administration on pregnancy outcome. Pregnant female Sprague-Dawley rats were randomly divided into four groups (eight rats/each), control group received distilled water, 2nd group treated with 8.8 mg of CdCl2/kg b. wt, 3rd group treated with 250 mg of Zingiber officinale/kg b. wt, and 4th group treated with 250 mg of Zingiber officinale/kg b. wt, followed by 8.8 mg of CdCl2/kg b.wt. Daily body weight of pregnant was recorded from GD1-GD20, and then pregnant rats were sacrificed at GD20. Samples of maternal and fetal livers and kidneys were processed for histological examination. Administration of Cd to pregnant rats showed adverse effects on pregnant mothers and their fetuses; reduced maternal weight gain, reduced absolute organ weights, reduced fetal growth parameters and placental weights together with altered histological appearance of the maternal and fetal livers and kidneys. While co-administration of Zingiber officinale showed an improvement of these toxic alterations. Zingiber officinale through its antioxidant activity could be beneficial against toxic outcomes of Cd exposure during pregnancy.
Food allergy has been long recognized and well documented. Other adverse reactions to foods first referred to as “toxic idiopathies” by John Freeman, co inventor of immunotherapy, at the early part of the 1900s can be mediated by and have their impact on the nervous and endocrine systems. It can also be mediated by pharmacologic mechanisms and can also affect any part of the body. There’s a great clinical need to accurately identify triggers of adverse reactivity as they have now been linked with even the most serious of modern maladies and diseases. In fact, inflammation is the hallmark of metabolic syndrome. Given the multitude of pathogenic mechanisms underlying adverse reactions to foods and other environmental exposures it is necessary that a utilizable and cost effective technology be understood so that its application be utilized under the appropriate circumstances.
KEY LEARNING POINTS
• The natural ability of certain foods to initiate an inflammatory response and induce metabolic disruptions and counterbalancing mechanisms to prevent that
• How foods can trigger “danger signals” for the immune system
Pharmacologic vs. immunologic reactions to foods
• Is there a common final pathway of all these mechanisms that can reliably indicate triggers of clinical pathology?
• Cellular testing vs. serologic testing: The advantages of cellular testing
Statement of Inger Mollerup, VP Novo Nordisk A/S for Congressional Hearings o...sstrumello
Statement of Inger Mollerup, MSc
Vice President Novo Nordisk A/S
Before the Government Oversight and Reform Committee Hearing On "Safe and Affordable Biotech Drugs - The Need for a Generic Pathway"
March 26, 2007
D-Penicillamine Alleviates Oxidative Stress in Neonates by Its Influence on C...inventionjournals
Objective – the aim of this article was to demonstrate the protection of biomembranes against lipid peroxidation, and highlight the role of D-Penicillamine (D-PA). Study Design – The authors conducted a review searching the relevant literature of bilirubin and copper metabolisms, and of antioxidant effects of D-PA in the neonatal period. Results – Unconjugated bilirubin has a special affinity for the globus pallidus, the hippocampus, and the subthalamic nucleus (basal ganglia). Furthermore, immaturity of the blood-brain barrier also contributes to the development of kernicterus. Homeostasis of metal ions usually involves a huge set of proteins which regulate the proper metal biology. Metal ions, especially copper and iron play very important roles in the pathogenesis of neurodegenerative diseases, including bilirubin-induced neurologic dysfunction (BIND), having impact on both protein structure (misfolding) and oxidative stress. D-PA by its ability to modulate both oxidative stress and nitric oxide (NO) pathway may have significant neuroprotective effects in cases jeopardized by BIND or retinopathy of prematurity (ROP). Interpretation – The authors conclude that treatment with D-PA might result in a wide range of health benefits, improved quality of life and reduced healthcare costs and may help reduce complications in the neonatal period. Keywords: Bilirubin-induced neurologic dysfunction; Reactive oxygen species; Copper dyshomeostasis;; Neurodegeneration; D-Penicillamine in the neonatal period Key points: ► D-PA was first recognized as a potential benefit for neonatal hyperbilirubinemia. During this time there was a remarkably low incidence ROP in the infants treated with this drug. Later, our studies were replicated in other institutes in Hungary, Poland, the USA, India and Mexico. ►It is important to note that there was no intolerance or short- or long-term toxicity of the medication, in spite of the fact that in the newborn period D-PA was used 10-20 times higher doses than those in adult. ► Metal ions, especially copper and iron play very important roles in the pathogenesis of neurodegenerative diseases, including BIND and ROP, having impact on both protein structure (misfolding) and oxidative stress. ► D-PA by its ability to modulate both oxidative stress and nitric oxide pathway may have significant neuroprotective effects in cases jeopardized by bilirubin encephalopathy or ROP
Who this is for: Health professionals.
Description: Dr. Sheila Bushkin-Bedient will be speaking on the prenatal origins of disease and why we should be focusing on studying possible connections between unconventional natural gas extraction and diabetes, obesity, and cancer.
About the Speaker: Sheila Bushkin is a member of the Institute of Health and the Environment at the State University at Albany, and Concerned Health Professionals of New York. She has been a member of the Medical Society of the State of New York for 15 years. Her specific areas of interest involve environmental health issues, chronic diseases, health concerns of older adults, and CME for physicians.
Gene–environment interactions in development and disease lovely - 2016 - wi...BARRY STANLEY 2 fasd
ETHANOL: THE EMPEROR OF ALL TERATOGENS
An account of gene/environment interaction in relation to the petro chemical age, and the historical significance of alcohol as teratogen.
Ameliorative potential of the quercetin on lead-induced testicular damage mor...Prof. Hesham N. Mustafa
Background
Quercetin, a naturally occurring flavonoid known for its potent antioxidant properties, has been investigated for its potential in counteracting the harmful effects of lead (Pb) toxicity, which induces apoptosis and oxidative damage in various human tissues. This study aims to assess the reparative effects of quercetin on lead-induced testicular damage.
Methods
Four groups, each comprising ten adult male albino rats, were randomly assigned as follows: Quercetin group, Pb group, Pb + Quercetin group, and control group. All treatments were administered orally via gavage daily for a duration of 30 days. Evaluation of sex hormone levels (serum testosterone, FSH, and LH), cytokines and inflammatory mediators (IL-1β, TNF-α, MCP-1), lead concentration, oxidative and antioxidant stress markers (superoxide anion [O2−], MDA, SOD, CAT, GSH), and sperm characteristics were carried out.
Results
The results demonstrated a significant decline in sex hormones and antioxidants, accompanied by an increase in lead concentrations, cytokines, inflammatory mediators, and oxidative stress indicators (O2−, MDA), while SOD, CAT, and GSH levels were reduced. The Pb-intoxicated group exhibited a substantial increase in dead and abnormal sperm, along with significant reductions in sperm concentration and motility. Morphometrically, a marked decrease was observed in spermatogonia, primary spermatocytes, spermatids, and sertoli cells per seminiferous tubule, as well as epithelial height. Furthermore, coadministration of quercetin exhibited notable benefits. It significantly elevated testosterone levels (P < 0.001), testicular SOD, CAT, and GSH activities, while decreasing MDA levels (P < 0.001). Quercetin also mitigated the deleterious effects of lead toxicity on sperm parameters and restored morphometric variations, including epithelial height.
Conclusions
Quercetin supplementation alongside lead exposure showed a potential for ameliorating degenerative changes caused by lead toxicity in the testicles. This cotreatment effectively reduced oxidative stress, cytokine levels, inflammatory mediators, and restored biochemical alterations, thereby improving morphometric parameters.
The pattern of branching and intercommunications of the musculocutaneous nerv...Prof. Hesham N. Mustafa
Background:
The aim of the present work was to provide evidence about the anatomical variations as regard the origin, distribution, and branching pattern of the musculocutaneous nerve (MCN).
Materials and methods:
Brachial plexus was dissected in 40 upper limbs of 20 male adult cadavers. The pattern of the musculocutaneous nerve was photographed by a digital camera.
Results:
The location and length of the nerve branches between left and right arms were recorded and statistically analyzed. In (90%) of specimens the MCN originates from the lateral cord of the brachial plexus, in (5%) it arose from the median nerve (MN), while in the remaining (5%) specimen, it was absent. The musculocutaneous nerve pierced the coracobrachialis muscle in 90% of specimens, and in the remaining (10%) did not pierce it. The motor branches to biceps brachii muscle were categorized into: Type 1 (90%): one branch that divides to supply the two heads of biceps; Type 2 (5%): double branches, innervating each head of biceps separately. The motor branches to brachialis muscle were categorized into: Type 1 (82.9%): one branch; Type 2 (14.2%): double branches and Type 3 (2.9%): three branches that innervating brachialis muscle. Communications between the MCN and the MN were observed in 35% of specimens.
Conclusions:
The knowledge of the common and uncommon musculocutaneous nerve variations is important especially to the surgeons for carrying out surgical procedures in axilla and arm.
Morphohistometric analysis of the effects of Coriandrum sativum on cortical a...Prof. Hesham N. Mustafa
Objective: Natural compounds can act as metal chelators and oxygen free radical scavengers, which allows them to be used as bioactive antagonists to heavy metals neurotoxicity. The aim of the study to analyze the morphometric effects of Coriandrum sativum (C. sativum) on lead-induced neurotoxicity.
Materials and Methods: Forty Sprague-Dawley albino rats were divided into four equal groups (ten in each group): control group; coriander group: received aqueous C. sativum extracts (600 mg/kg BW for 60 days orally); lead (Pb) group: received a daily dose of lead acetate (Pb) (10 mg/kg BW for 60 days orally); Pb+ coriandrum group: received: aqueous C. sativum extract (600 mg/kg BW) prior to 10 mg/kg BW of Pb. The following parameters malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. Layers thickness and nuclei density were analyzed.
Results: Lead levels in blood and tissues were decreased significantly in the Pb group and those findings were corrected significantly (p=0.001) with C. sativum addition. Data exhibited an increase in oxidative stress marker MDA and a decrease in antioxidant enzymes activities (SOD, CAT, and GPx) significantly in the Pb group and those effects were reversed significantly (p=0.001) by C. sativum administration. The cerebellar cortex and all layers of the somatosensory cortex thickness and nuclei density were diminished significantly in the Pb group. The morphometrical measurements were corrected significantly (p=0.001) by C. sativum.
Conclusion: From the findings of the current study, Pb caused noticeable structural and functional variations in the cerebellar cortex and somatosensory cortex. C. sativum corrected these parameters as it possesses chelating and antioxidant potentials.
Background:
The anterolateral ligament (ALL) is a true well-defined ligament in the knee first described in 1879 by Segond. After the work of Claes et al., several studies were conducted about biomechanics and its role in stability of the knee. The anatomical existence of the ALL has been studied by and various radiographic diagnostic modalities and in cadavers. It originates from lateral femoral epicondyle and is inserted between Gerdy’s tubercle and the fibular head. There has been controversy about the existence of ALL in pediatric patients. The aim of this work was to confirm the presence of ALL in pediatric patients by using MRI.
Materials and Methods:
We reviewed the knee MRI scans of 100 pediatric patients (ages between one and 12 yr) who had no knee injury or congenital deformity and had been evaluated by an expert radiologist.
Results:
The ALL was detected in 90% of the pediatric patients with the use of MRI.
Conclusions:
The main finding of this study was that ALL can be seen in pediatric patients using MRI. Despite numerous studies, additional research is needed to further define the role of the ALL in knee function.
Level of Evidence:
Level IV.
Protective role of co q10 or l carnitine on the integrity of the myocardium i...Prof. Hesham N. Mustafa
Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.
Keywords: Cardiotoxicity; CoQ10 and L-carnitine; Dox; Vimentin; eNOS.
One year mortality rate after hip fracture in the western region of saudi ara...Prof. Hesham N. Mustafa
Background:
The mortality rate of elderly patients who sustain a hip fracture is high compared to the general population. Identifying risk factors can help predict patients at risk of hip fracture to reduce the mortality rate. No studies have shown the mortality rate of patients with hip fractures in the western region of Saudi Arabia. Therefore, this study aimed to identify the risk factors associated with the mortality of patients with hip fractures admitted to the King Abdulaziz Hospital and compare the results with other studies.
Methods:
The mortality rate (within 1 yr or less) in 177 patients over the age of 60 yr who were admitted to the university hospital between July, 2007, and September, 2012, with hip fractures was retrospectively studied. The patients were assessed with regard to gender, age, type of hip fracture, and type of surgical intervention.
Results:
The overall mortality rate 1 yr after hip fracture was 12.43%, and the mean age was 77.77 yr old. The risk factors most associated with mortality were as follows: advanced age (71 to 80 and 81 to 90 yr old), male, peritrochanteric (extracapsular) fracture, and operative fixation with dynamic hip screw.
Conclusions:
The mortality rate of patients with hip fractures within 1 yr has a high-risk potential, especially for male patients over 71 yr of age with peritrochanteric (extracapsular) fractures. Surgical treatment with dynamic hip screw also was shown to be a risk factor between the different treatment options.
Level of Evidence:
Level IV.
Biomarkers of Systemic Lupus Erythematosus and Systemic Sclerosis diseases ac...Prof. Hesham N. Mustafa
Systemic Lupus Erythematosus (SLE) and systemic sclerosis (SSc) are systemic inflammatory autoimmune disorders characterized by a large spectrum of clinical and laboratory features. The aim of the present study was to investigate the possible use of serum level of soluble intercellular adhesion molecule-1(sICAM-1) and soluble interleukin-2 receptor (sIL-2Ra) as biomarkers for monitoring of SLE and SSc disease activity. Moreover, it aimed to compare the specificity and sensitivity as well as cut-off value of both biomarkers in a sample of Egyptian patients. 50 SLE patients, 30 SSc patients and 60 age and sex matched healthy controls were enrolled in our study. sICAM-1and sIL-2Ra were measured in serum samples obtained from all participants. In addition to Erythosedimentation rate (ESR), complete blood count (CBC), Antineuclearantibodies (ANA) estimation, disease activity of both diseases were also assessed. sICAM-1and sIL-2Ra levels were higher in SLE and SSc patients versus control. Both parameters are correlated with each other as well as the activity parameters. A cut-off levels of 455.59 (ng/ml) &2525935 (pg/ml) in both SLE & SSs respectively was observed with the highest specificity and sensitivity. It could be concluded that sICAM-1 and sIL-2Ra are noninvasive biomarkers for SLE and SSc that could play a pathophysiologic role in development and progression of both diseases. Moreover, sICAM-1 and sIL-2Ra are correlated with the disease activity at cut-off values of 455.59 (ng/ml) & 2525935(pg/ml) respectively.
Morphohistometric study of the ligamentum flavum in cervical,thoracic and lum...Prof. Hesham N. Mustafa
ABSTRACT Anatomic characterization and fine structure of the human ligamentum flavum (LF), especially at different spinal levels, represent an attractive focus for the scientific and surgical application. Descrip-tive anatomical and structural study of LF at the cervical, thoracic and lumbar levels of the vertebral column in human cadavers is carried out here. The aim of the work is to clarify the anatomical features and fine structural differences in the human LF at different vertebral levels (cervical, thoracic and lumbar). Specimens of vertebral column were ob-tained from 34 human preserved cadavers. Their average age ranged between 56 and 69 years. Morphometric parameters including height, width and thickness of the ligament flavum at the mid-levels of cervical, thoracic and lumbar regions were measured. Sections obtained from different levels were stained with different stains. Morpho-metric measurements involved the relative elastic area, relative collagen area, elastic area% and collagen area% were measured.The results of the height, width and thickness of the LF at different spinal levels showed gradual increase in their mean values respectively. The LF midline gaps were found in the cervical, thoracic and lumbar regions. The morphometrical measure-ments showed that the average elastic area was highest in the cervical region and lowest in the tho-racic region. In the lumbar region, the percentages of both elastic area and the collagen area were nearly the same. The characterization of morpho-logical and histological aspects of the LF at differ-ent spinal levels will be of great importance for ap-plications in spinal surgery, biomechanical and physical rehabilitation of vertebral column.Keywords: Ligamentum Flavum – Spinal – Collagen and elastic fibers
Correlation between acl injury and involvement of the anterolateral ligament ...Prof. Hesham N. Mustafa
Background:
Clinical testing has demonstrated the role of the anterolateral ligament (ALL) in controlling anterolateral laxity and knee instability at high angles of flexion. Few studies have discussed the association between an anterior cruciate ligament (ACL) injury and ALL injury, specifically after residual internal rotation and a post-ACL reconstruction positive pivot-shift that could be attributed to ALL injury. The goal of this study was to assess the correlation between ALL injury and ALL injury with concomitant ACL injury using MRI.
Material and Methods:
This was a retrospective study of 246 patients with unilateral ACL knee injuries from a database that was reexamined to identify whether ALL injuries occurred in association with ACL injuries. We excluded the postoperative reconstructed cases. The charts were reviewed on the basis of the presence or absence of diagnosed ACL injury with no regard for age or sex.
Results:
Of the 246 patients with ACL injury, there were 165 (67.1%) patients with complete tears, 55 (22.4%) with partial tears, and 26 (10.6%) with sprains. There were 176 (71.5%) patients with ALL and associated ACL injuries, whereas 70 (28.5%) did not have associated ACL injuries. There was a significant statistical relationship between ACL and ALL injuries (P<0.0001).
Conclusions:
There is high incidence of ALL tears associated with ACL injuries. Clinicians should be aware of this injury and consider the possibility of simultaneous ALL and ACL repair to prevent further knee instability.
Level of Evidence:
Level IV.
Liver ischemia/reperfusion injury, a setting in which the functional mass is ...Prof. Hesham N. Mustafa
Liver ischemia reperfusion is induced during sur-gical procedures like liver transplantation and re-section. Multiple mechanisms have been postulat-ed to liver damage following liver ischemia reperfu-sion injury, such as oxidative stress and inflamma-tory reactions. The present study declares the pos-sible mechanism of tadalafil, toward modulating the inflammatory response. Forty-eight rats were divided into 4 groups as follows; Sham group sub-jected to midline laparotomy only. Tadalafil group administered Tadalafil 10 mg/kg intraperitoneal 45 min before sham operation. I/R (Ischemia-reperfusion) group, rats undergo 60 min of hepatic ischemia followed by 60 min of reperfusion. Tada-lafil + I/R group rats undergo a similar pattern of I/R after the treatment with Tadalafil 10 mg/kg, 45 min before ischemia. At the end of the reperfusion, the blood samples were collected for estimation of biochemical markers including liver enzymes using colorimetric assay method and serum: TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) le-vels, ICAM- 1 (Intercellular Adhesion Molecule-1) were measured. Tissues were evaluated by semi-quantitative and morphometrical approaches. Ta-dalafil succeeded in restoring normal levels of liverenzymes and ameliorating the oxidative stress as evidenced by decreasing MDA and restoring redu-ced glutathione levels in liver tissue homogenate. Also, Tadalafil exhibits anti-inflammatory effects, as it significantly decreased the levels of TNF-α, IL6 and ICAM-1. The findings are supported by BCL-2, TNF-α immunomarkers. It is concluded that modulation of the inflammatory response might be one of the mechanisms of Tadalafil-mediated he-patoprotection, so it is recommended as an adju-vant therapy in liver surgery.Keywords: Ischemia/reperfusion injury – Oxidative stress – Apoptosis – TNF-α – BCL-2
Neuro-amelioration of cinnamaldehyde in aluminum-induced Alzheimer’s disease ...Prof. Hesham N. Mustafa
Aluminum (Al) is a neurotoxic substance which has played an important role in the etiology, pathogenesis, and development of amyloid-β (Aβ) plaques. This study was carried out to evaluate the neuroprotective effect of aqueous cinnamon extract against aluminum chloride (AlCl3)-induced Alzheimer’s disease. Forty adult male albino rats, randomly divided into four equal groups. Control group; ACE200 group administered aqueous cinnamon extract (ACE) orally; AlCl3 group received daily intraperitoneal (i.p.) injection of AlCl3 for 60 days to induce neurotoxicity and AlCl3 + ACE200 group received a combination of AlCl3 and ACE in the same dose and route as previous groups. Aluminum administration significantly enhanced the memory impairment and the Aβ formation in the rat model. The cerebellum exhibited a significant reduced number of Purkinje cells, marked decrease in the density of dendritic arborization and prominent perineuronal spaces in the molecular layer. There was loss of dendritic spines, neurofibrillary degeneration, and appearance of neuritic plaques. Concomitant administration of AlCl3 and ACE displayed an observable protection against these changes with progressive improvement in memory and intellectual performance. In conclusion, ACE may play a protective role against formation of amyloid-β plaques in cerebellum.
Analytical Study of Clinicopathological Data of Saudi Patients with Osteoarth...Prof. Hesham N. Mustafa
SUMMARY: Knee osteoarthritis (OA) is a common disabling disease. Epidemiological studies have revealed various risk
factors for OA, including sex, aging, obesity, occupational illnesses, and chronic diseases. Here we evaluate the clinical, pathological,
and radiological findings of knee OA in a subset of Saudi patients who were subjected to total knee replacement (TKA). The study
population included 30 Saudi patients with knee OA who were operated by TKA (from June 2014 to December 2015) in the Department
of Orthopedics, Faculty of Medicine, King Abdulaziz University, Saudi Arabia. Patient’s clinical and radiological data were collected
from the hospital files. Pathological examination of the excised superior articular surface of tibia and femoral condyles were done.
Pearson Chi-squared analysis was used to test for differences between the variables in associated risk factors. There were more women
than men. Sixty per cent of patients were older than 60 years [mean age, 59.2 (females) and 61.7 (men) years-old]. All patients exceeded
obesity class 1, with females being more obese than males. Pathological examination of the superior articular surface of tibia and femoral
condyles showed high score lesions, which was more apparent in females than in males. Radiological findings showed that most lesions
were high grade. The findings of this study will help to understand the pathogenesis of OA and improve treatment decision making
relevant to TKA in knee OA in Saudi Arabia and elsewhere.
KEY WORDS: Osteoarthritis; Knee; Arthroplasty.
A Study on the Toxic Effect of Different Doses of Diclofenac Sodium on the De...Prof. Hesham N. Mustafa
SUMMARY: The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by
morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and
divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9
mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth
were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin
and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels,
increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group.
Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects
that are dose-dependent in the prenatal subjected kidney to this drug.
KEY WORDS: Diclofenac sodium; Proximal convoluted tubules; Apoptosis;Cyclooxygenase.
A study on the toxic effect of different doses of Diclofenac sodium on the de...Prof. Hesham N. Mustafa
The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9 mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels, increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group. Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects that are dose-dependent in the prenatal subjected kidney to this drug.
Keywords : Diclofenac sodium; Proximal convoluted tubules; Apoptosis; Cyclooxygenase.
Evaluation of the safety of conventional lighting replacement by artificial d...Prof. Hesham N. Mustafa
Background
Short morning exposure to high illuminance visible electromagnetic radiations termed as artificial daylight is beneficial for the mental health of people living in geographical areas with important seasonal changes in daylight illuminance. However, the commercial success of high illuminance light sources has raised the question of the safety of long hour exposure.
Methods
We have investigated the effect of the replacement of natural daylight by artificial daylight in Swiss mice raised under natural lighting conditions. Mice were monitored for neurotoxicity and general health changes. They were submitted to a battery of conventional tests for mood, motor and cognitive functions’ assessment on exposure day (ED) 14 and ED20. Following sacrifice on ED21 due to marked signs of neurotoxicity, the expression of markers of inflammation and apoptosis was assessed in the entorhinal cortex and neurons were estimated in the hippocampal formation.
Results
Signs of severe cognitive and motor impairments, mood disorders, and hepatotoxicity were observed in animals exposed to artificial daylight on ED20, unlike on ED14 and unlike groups exposed to natural daylight or conventional lighting. Activated microglia and astrocytes were observed in the entorhinal cortex, as well as dead and dying neurons. Neuronal counts revealed massive neuronal loss in the hippocampal formation.
Conclusions
These results suggest that long hour exposure to high illuminance visible electromagnetic radiations induced severe alterations in brain function and general health in mice partly mediated by damages to the neocortex-entorhinal cortex-hippocampus axis. These findings raise caution over long hour use of high illuminance artificial light.
The Ameliorative Potential of Dexmedetomidine and Benincasa Cerifera Extract ...Prof. Hesham N. Mustafa
Renal ischemia/reperfusion injury (IRI) represents the main reason for acute kidney injury (AKI). Dexmedetomidine (Dex) and Benincasa cerifera (BC) have wide benefits due to their anti-inflammatory and antioxidant properties. This study aims to illustrate the protective effects of BC and Dex on renal IRI in a diabetic model. Sixty adult male albino rats (Wistar strain), weighing 250–300 g, were included in the study. The rats were divided into four groups, as follows: sham group: (non-diabetic); diabetes mellitus (DM) + IRI group: streptozotocin (STZ)-induced diabetic rats exposed to renal IRI on day 30 after diagnosis of diabetes; DM + IRI + BC group: STZ-induced diabetic rats treated with BC (500 mg/kg) for 30 days after diagnosis of diabetes, then exposed to renal IRI; and DM + IRI + Dex group: STZ-induced diabetic rats treated with Dex (100 µg/kg intraperitoneally) 5 min before induction of ischemia on day 30 after diagnosis of diabetes, then exposed to renal IRI. Biochemical parameters, histopathological examination, and immunohistochemical markers were evaluated. A significant improvement in the biochemical, histopathological, and immunohistochemical parameters were observed in the DM + IRI + BC group, while the DM + IRI + Dex group showed improvements in renal IRI and dyslipidemia. The present study demonstrated that oxidative stress plays a chief role in renal IRI in the STZ-induced diabetic model. Treatment with BC achieved excellent ameliorative effects, while treatment with DEX improved renal IRI.
Keywords:
Diabetes; Dexmedetomidine; Ischemia/Reperfusion; Oxidative Stress
Immunohistochemical Study of the Ameliorative Effect of Vitamin E on Liver Re...Prof. Hesham N. Mustafa
The liver is almost unique in its capacity for regeneration after hepatectomy but the exact mechanisms are not yet fully clarified. Antioxidants have been shown to promote liver regeneration after major hepatectomy. The present study evaluated the ameliorative effect of vitamin E administration on the liver regeneration after different periods of partial hepatectomy (PH) in rats. Fifty-six adult male albino rats were divided into three groups: Control sham operated group; partially hepatectomized group which were divided into three subgroups sacrificed at 1day, 3 days and 7days after the operation respectively; Partially Hepatectomized group with vitamin E pretreatment before PH where the rats were given a daily oral dose of vitamin E until the time of sacrifice of the rats. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and labeling index were demonstrated. After PH, the PCNA positive hepatocytes and the PCNA labeling indices were significantly high after the 1st day and then much decreased after the 3rd day, to be followed by a slight increase at the 7th day. Vitamin E pretreatment in PH rats resulted in a decrease in PCNA positive cells and its labeling indices in the 1st day with a gradual increase in the 3rd and 7th days. Vitamin E has an inhibitory effect in the first 24 hours on liver regeneration followed by stimulatory effect at the third and seventh days after PH. These data indicated that vitamin E pretreatment has an important role in regulation and enhancement of liver regeneration after PH.
Keywords:
Immunohistochemistry; Labeling Index; Vitamin E; Partial Hepatectomy; PCNA
The role of curcumin in streptozotocin induced hepatic damage and the trans-d...Prof. Hesham N. Mustafa
Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.
Does allicin combined with vitamin B-complex have superior potentials than al...Prof. Hesham N. Mustafa
BACKGROUND:
The current article aims to explore the protective potentials of α-tocopherol alone and the combination of allicin and vitamin B-complex against lead-acetate neurotoxicity on the cerebellar cortex.
MATERIALS AND METHODS:
Forty rats were divided into four groups (n=10). Group 1 was the control group. Group 2 received 10 mg/kg body weight (BW) of lead acetate. Group 3 was exposed to 10 mg/kg BW of lead acetate plus a combination of allicin (100 mg/kg BW) and vit. B-complex (40 mg/kg BW). Group 4 was administered lead acetate (10 mg/kg BW) and α-tocopherol (100 mg/kg BW). The animals received treatment for sixty days by oral gavage. All the groups were studied ultrastructurally and immunohistochemically with glial fibrillary acidic protein (GFAP).
RESULTS:
The affected groups revealed shrunken and degenerated Purkinje cells with irregular nuclei. The cytoplasm comprised several lysosomes, unhealthy mitochondria, and dilated Golgi saccules. The myelinated nerve fibers demonstrated breaking of the myelin sheaths, apparent vacuoles, and broad axonal spaces. Immunohistochemically, there was a tremendous surge in GFAP-positive astrocytes in the lead acetate-treated group. These histological and ultrastructural variations were ameliorated by the administration of α-tocopherol and the combination of allicin and vit. B complex. Moreover, an apparent decrease in the number of GFAP-positive astrocytes was obvious in the protected groups.
CONCLUSIONS:
Although both α-tocopherol and the combination of allicin and vit. B-complex can be used as possible adjuvant therapies to ameliorate nervous system ailments attributable to lead acetate, α-tocopherol showed more protective potential.
KEYWORDS:
Allicin; Astrocytes; GFAP; Myelin Figure; Oligodendrocyte; Purkinje cells
Potential Alleviation of Chlorella vulgaris and Zingiber officinale on Lead-I...Prof. Hesham N. Mustafa
Natural products were studied to combat reproductive alterations of lead. The current work
aimed to disclose the efficacy of Chlorella vulgaris and Zingiber officinale to alleviate lead
acetate induced toxicity. Sixty adult male Wistar rats were distributed into four groups.
Group 1 was considered control, group 2 received 200 mg/l PbAc water, group 3 received 50
mg/kg/rat of C. vulgaris extract and 200 mg/l PbAc water, and group 4 received 100
mg/kg/rat of Z. officinale and 200 mg/l PbAc water for 90 days. Testis samples were subjected
to ultrastructural examination. It was observed that PbAc caused degenerative alterations in
the spermatogenic series in many tubules, with a loss of germ cells and vacuoles inside the
cytoplasm and between the germ cells. Mitochondria exhibited ballooning, with lost cristae
and widening of the interstitial tissue, while nuclear envelopes of primary spermatocytes
were broken up, and axonemes of the mid-pieces of the sperms were distorted. With the
treatment with C. vulgaris or Z. officinale, there were noticeable improvements in these
modifications. It was concluded that both C. vulgaris and Z. officinale represent convincing
medicinal components that may be used to ameliorate testicular toxicity in those exposed to
lead in daily life with superior potentials revealed by C. vulgaris due to its chelating action.
Key words: Chlorella vulgaris, lead acetate, ultrastructure, Zingiber officinale.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
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Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
2. 872 Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
and gastrointestinal tracts where it is transported
to different tissues 2
.
Although Pb has a wide range of impacts
on body system toxicities, its neurotoxic effect
is the most prominent. It has been described that
cerebrum is a vulnerable target to Pb cause it
contains low levels of enzymes that are responsible
for defending it against oxidative stress and
because of its high myelin-related content, which
increases the vulnerability to peroxidation 3
.Also,
it has been stated that Pb can interrupt the structure
of the blood-brain barrier by destructing endothelial
and glial cells and disturbing the building of tight
junctions between barrier cells 4
.
Recently, Pb developmental toxicity
has occurred as a major health problem for
pregnant cause the fetus is vulnerable to Pb’s
many toxic agents 5
. Gestational Pb exposure
produces toxic effects, that include teratogenesis,
risk of low birth weight and reduced mental
development 6
. Moreover, studies have proved that
developmental Pb exposure exerts neurotoxicity
during differentiation, synaptogenesis, and end-
stages of brain development 7
.
Accumulating data supporting the role
of oxidative stress in the pathophysiology of Pb
toxicity has recently been reported. Pb can induce
oxidative damage to cellular components involved
in the production of reactive oxygen species (ROS).
The mechanisms for Pb-induced oxidative stress
may be either direct or indirect by uprising the
creation of lipid peroxidation to levels that can
disturb cell membrane functions, lipid metabolism
and the antioxidant defense systems of cells 8, 9
. In
addition, interruption of the prooxidant/antioxidant
balance via excessive production of ROS have a
significant role in brain pathology 10
. The effect
of Pb on fetal growth has caused great concern as
many studies have reported shortfalls in prenatal
development in cases where mothers were exposed
to high Pb levels during their pregnancies. Also, it
is worth mentioning that Pb exposure during early
childhood has been described to cause various toxic
effects in both humans and animals 11
. The effects
of Pb on pregnancy and the fetus are complex and
not completely understood in cases where both
the mother and her fetus are victims of high Pb
exposure. It has been proven that Pb can cross the
placenta, and there is a positive correlation between
Pb levels in both maternal and umbilical cord
blood 12
.
In the last few years, greater attention has
been given to the curative potentials of medicinal
plants as natural antioxidants, due to their lack
of side effects and low cost. Also, many clinical
studies have suggested that the antioxidants in
fruits and vegetables are key in minimzing many
chronic diseases incidence 13
. One of these plants is
curcumin (Cur) 14
, which is a famous, biologically
active phenolic compound that is a chief element
in turmeric, a yellow spice that is removed
from the rhizome of Curcuma longa L. (family
Zingiberaceae) 15, 16
. Cur exhibits limited solubility
in water and good solubility in chloroform and
dimethyl sulfoxide (DMSO), which may be
account for its low bioavailability 17
.
Cur is reported to have many therapeutic
features, including anti-inflammatory 18
,
hypoglycemic 19
, hypocholestrolemic 20
, chelating
21
, and antioxidant 22-24
. The antioxidant property of
Cur is due its effective scavenging of ROS. It also
decreases the level of lipid peroxides and augments
the activity of antioxidant enzymes 25
. Some
studies have reported that Cur could protect against
different brain disorders and neurodegeneration
through suppression of oxidative stress 26-28
.
Cur has been used for a long time as a
traditional medication during pregnancy, and no
medical authority recommends against its use 29
. It
is beneficial in treating several disorders that occur
commonly in pregnant women, such as anorexia,
coryza, cough, and sinusitis 26-28, 30
. Cur is highly
lipophilic and is capable of crossing the blood-brain
barrier, as confirmed by its high concentration in
the fetal brain after oral intake 31
. The current study
was intended to investigate the protective role
of Cur against maternal and fetal developmental
parameters, oxidative stress, and cerebral damage,
which was produced by two doses of Pb during
pregnancy.
MATERIALand METHODS
Chemicals
Lead acetate (PbAc) pure crystals with a
molecular weight of 379.33 and analytical-grade
were purchased from Sigma Chemical Company
(USA), and other chemicals and staining reagents
3. 873Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
used in this study were purchased through local
scientific agents in Jeddah, Saudi Arabia.
Animals and experimental work
Adult, sexually mature nulliparous female
Sprague-Dawley albino rats (weighing 200-225
grams at the beginning of the experiment) were
used in this study. They were obtained from the
Animal House of King Fahd Medical Research
Center. All experimental procedures were carried
out in accordance with the international guidelines
for the care and use of animals in the laboratory.
This study was approved and registered by the
Committee of Animal Investigations, Faculty of
Medicine, King Abdulaziz University. During the
study, the female rats were kept in separate metallic
cages under standard temperature (24 ± 2ºC),
humidity (55 ± 5%), and lighting (12h:12h light/
dark) conditions. They were fed a standard chow
diet ad libitum and had free access to water. After
acclimatization for two weeks, mating procedure
was conducted by placing the individual females
overnight in the home cage of a singly-housed male
of the same stock. Gestation was confirmed by
positive identification of spermatozoa in a vaginal
lavage smear; the day of confirmation is designated
as gestation day 0 (GD0), with subsequent days of
gestation numbered accordingly 32
. Only positively
pregnant females were chosen and randomly
divided into the following seven groups (eight-rats
each):
• Group I: the female rats were treated with
deionized water only from GD 1-20 of pregnancy
(control group) through oral gavage.
• Group II (Cur): the female rats were
treated with Cur at doses of 300 mg/kg b.wt.
through oral gavage once a day from GD 1-20 of
pregnancy.
• Group III (DMSO): the female rats were
treated with 50% DMSO (solvent of Cur) through
oral gavage once a day from GD 1-20 33-35
.
• Group IV (L160): the female rats were
given 160 ppm of Pb acetate (PbAc) through oral
gavage once a day from GD 1-20.
• Group V (L160 + Cur): the female rats
were given 160 ppm of PbAc plus Cur (300 mg/kg
b.wt.) by oral gavage once a day from GD 1-20.
• Group VI (L320): the female rats were
given 320 ppm of PbAc by oral gavage from GD
1-20.
• Group VII (L320 + Cur): the female rats
were given 320 ppm of PbAc plus garlic extract
(300 mg/kg b.wt.) by oral gavage once a day from
GD 1-20.
Pb solution was prepared by dissolving
PbAc in acidified, distilled water in concentrations
of 0.1 and 0.2% (w/v), containing 160 and 320 ppm
of Pb respectively 36
. Cur solution was prepared
by dissolving the powder in 50% DMSO to give a
dose of 300 mg/kg body weight and diluted further
with distilled water in 1.0 ml volume; this was
administered orally once a day 37
.
Evaluations of pregnant rats and fetuses
The pregnant female rats of each group
were observed daily throughout gestation for
mortality, morbidity, and body-weight gain
following treatment. On day 20 of gestation and
under ether anesthesia, blood samples were taken
via cardiac puncture and centrifuged at 3,000 rpm
for 15 minutes to separate the sera, which were
stored at -80°C. Then, the abdominal cavity was
opened, the gravid uterine horns were removed
and weighed, and the uterine contents were
examined to determine the number of corpora lutea,
implantation sites, and resorptions (embryonic
death); also, the number and position of viable
and dead fetuses were counted. Additionally, pre-
implantation losses were calculated as: (number
of corpora lutea – number of implantations) ×
100 / number of corpora lutea. Then, all viable
fetuses and placentas were removed and weighed
separately. Following this, fetal crown-rump
length, head length, and biparietal diameter were
measured using a Vernier caliper and recorded. The
heads of the mother and fetal rats of each group
were opened, and the cerebellum of mother and
fetal brains were quickly extracted and weighed.
All extracted specimens were divided sagittally
into two halves; the right halves were fixed in
10% neutral-buffered formalin for histological and
immunohistochemical study, and the left halves
were frozen and stored at -70°C.
Measurement of Pb levels in the brain tissues
Left halves of the brains from rat
mothers and fetuses of all groups were digested in
concentrated HNO3
Suprapur in a shaking water
bath at 60°C for 30 minutes. After digestion, the
solution was diluted (1:5 v/v) with deionized water.
Pb levels were measured using a graphite furnace
atomic absorption spectrophotometer (Perkin-
Elmer Model 3030) at King Fahd Medical Research
4. 874 Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
Center, King Abdulaziz University. Results were
expressed as µg of Pb/dl blood, and Pb levels in
brain and placenta were expressed as µg/g tissue
weight 36, 38, 39
.
Biochemical assays
Left halves of the brains from rat mothers
and fetuses of all groups were homogenized
(10% w/v) in ice-cold 0.1 M sodium phosphate
buffer (pH 7.4). The homogenate was centrifuged
twice at 4,000 rpm for 15-20 minutes at 4°C. The
resultant supernatant was used for estimation of
various biochemical assays. The lipid peroxidation
(LPO) was estimated by determining the amount
of malondialdehyde (MDA), a product formed
due to the peroxidation of membrane lipids using
a thiobarbituric acid-reactive substances assay
kit (BioAssay Systems, Hayward, CA) 40
. The
antioxidant enzyme activity of the rat brains was
evaluated by determining the superoxide dismutase
(SOD) activity. This was measured using a SOD
assay kit (Cayman), in which a tetrazolium salt
was used for detection of superoxide radicals
generated by xanthine oxidase and hypoxanthine 41
.
Catalase (CAT) activity was assayed according to
the peroxidatic function of catalase using a catalase
assay kit (Cayman) 41
. Glutathione peroxidase
(GPx) activity was assayed by coupling the enzyme
procedure with glutathione reductase using a GPx
assay kit (Cayman) 41
.
Histological and immunohistochemical methods
The fixed right halves of the maternal
and fetal brains of all experimental groups were
dehydrated, cleared, and embedded in paraffin,
and then sections of 5 um thickness were cut.
Some sections were stained with hematoxilin-eosin
(H&E)forgeneralexamination.Othersectionswere
immunohistochemically stained with a modified
avidin-biotin peroxidase technique for anti-GFAP
to examine the astrocytes. Deparaffinized and
rehydrated sections were treated with 0.01 M
citrate buffer (pH 6.0) for 10 minutes to unmask
antigens, and then incubated with a monoclonal
antibody against GFAP (1:100 monoclonal mouse
anti-GFAP) for 18-20 hours. Detection of the
antibody was carried out using a biotin-streptavidin
detection system with 0.05% diaminobenzidine as
a chromogen and counterstained with hematoxylin.
GFAP-positive cells appeared brown and their
nuclei appeared blue. The positive results were
indicated by brown coloration of the cell membrane
and cytoplasm of the astrocytes. Finally, all slides
were examined with an Olympus BX53 microscope
equipped with a camera (Olympus, Tokyo, Japan)
at different magnifications 42
.
Quantitative Morphometric study
Ten slides of non-overlapping fields from
each group (at least five animals/group), at least
one slide from each animal, were analyzed with the
use of Image-Pro Plus v6 (Media Cybernetics Inc.,
Bethesda, Maryland, USA) and Image J (National
Institute of Health, USA) was used to quantify
cells, measure area% covered by cells and colour
intensity (GFAP immunoreaction in astrocytes)
within the cerebral cortex. All morphometric
measurements were done at x100 magnification
42, 43
. For each calculation, the background was
determined by manually adjusting the density
window of the system until only the GFAP-positive
tissue was selected. i.e. Digital brightfield images
were uploaded into the image J software and scale
set using a digital micrcrometer gauge reading to
convert measurements in pixels to microns, and
this was applied to all images. Cells were counted
using the cell-counter plug-in available on the
image J software after a grid had been applied
across the image; number of different cell types
in the respective brain regions was then counted.
Total number of cells, area% covered by cells
and average cell size were calculated using the
automated cell-counter after thresholding for
colour. Then, immunoreactive blood vessels,
nonspecific staining, and artifacts were omitted
before quantitation. When a subfield was too large
to be analyzed at one time, several measurements
of non-overlapping areas were made and then
averaged. For whole cortex, the GFAP-positive
area was divided by the total area analyzed to obtain
an estimate of the area% occupied by astrocytes
and their processes 43-45
.
Statistical analysis
All the data were presented as mean ±
standard deviation of studied parameters from
each group. Data were analyzed using a one-way
analysis of variance followed by Bonferroni’s post
hoc test or Student’s t-test, wherever applicable.
Four different maternal and fetal parameters were
used. All statistical analyses were done using the
Statistical Package for the Social Sciences (SPSS,
version 23) (USA). The values of P < 0.05 were
considered significant.
5. 875Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
RESULTS
Maternal findings
During the experiment, two pregnant
rats from the high-dose Pb-treated group died.
Post-mortem examination revealed that the fetuses
aborted or died, and the treatment had no effect
on the duration of the pregnancy. As represented
in Table 1, there was a significant reduction in
both maternal weight gain and placental and brain
weights in Pb-treated groups, which was more
marked in the group that received the larger Pb
dose, when compared to the control. Also, it was
noticed that the co-administration of Cur improved
these effects.
Fetal findings
As seen in Table 2, the Pb-treated groups
displayed a reduction of fetal weight and other
fetal growth parameters (crown-rump length,
head length, biparietal diameter, umbilical cord
length), which was more marked in the group that
received the larger Pb dose, when compared to the
control; the co-administration of Cur along with Pb
improved these effects.
Materno-fetal Pb analysis
The data in Table 3 show that there were
parallel and significant increases in the mean values
of Pb-level concentrations in the maternal blood
and brains and fetal brains in Pb-treated groups
than in the control group; this was higher in the
group that received the larger Pb dose. Also, co-
administration of Cur along with Pb resulted in the
reduction of Pb levels versus the control group.
Analysis showed that Pb content in the fetal brain
was positively correlated to maternal Pb levels,
which indicates Pb transfer from the mother to the
fetus.
Biochemical assays
As seen in Table 4, there was a significant
increase of MDA levels in the maternal brains of
Pb-treated groups, which was significant when
compared to the control group; this was higher
in the group that received the larger Pb dose.
Moreover, there was a decrease of SOD, CAT,
and GPx levels in Pb-treated groups in a dose-
dependent manner, which was significant when
compared to the control group. Co-administration
of Cur along with Pb resulted in the decrease of
Fig. 1. Photomicrographs of cerebral cortex from control and Cur treated mother rats showing A & B) the normal
layering pattern in the form of six layers; I: outer molecular layer, II: external granular layer, III: external pyramidal
layer, IV: inner granular layer, V: inner pyramidal layer, VI: polymorphic layer. C) the pyramidal cells (P) with
their multipolar shape, vesicular nuclei and basophilic cytoplasm. Granular cells (G) were seen with large nuclei,
prominent nucleolus and little cytoplasm. The smaller neuroglia cells are scattered (↑). D) a few GFAP positive
astrocytes with brown cytoplasmic granules (↑). pm= pia matter, bv= blood vessel. [A, B & C: H & E X 100, 200
& 400, D: GFAP X 200]
6. 876Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
Fig. 2. Photomicrographs of cerebral cortex from
low dose Pb-treated mother rats showing A) a little
disorganization of cortical layers with some congested
blood vessels (bv). B) some shrunken pyramidal cells
(P) with loss of their processes, dark cytoplasm and
small darkly stained nucleus. Some granular cells (G)
are surrounded with halos. C) an increase in the GFAP
immunoreactive astrocytes (↑) as compared to the control
group. pm= pia matter [A&B: H&E X100 & 400, C:
GFAP X 200]
Fig. 3. Photomicrographs of cerebral cortex from high
dose Pb-treated mother rats showing A) a distortion
and disappearance of normal arranged cortical layers
with dilated blood vessels. B) some pyramidal cells (P)
were appeared darkly stained and irregular in shape with
pyknotic nuclei; other cells showed marked vacuolization
with faintly stained cytoplasm. Notice that some granular
cells are shrunken and deeply stained (G). C) a marked
increase in the number of GFAP immunoreactive
astrocytes (↑) as compared to low dose Pb treated and
control groups. pm= pia matter, bv= blood vessel. [A&B:
H&E X100 & 400, C: GFAP X 200]
MDAlevel and the increase of antioxidant enzyme
activities.
Regarding the fetal brains, Table 5
illustrates that there was a significant increase
7. 877 Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
Table 1. Effect of gestational Pb and Cur co-administration
on pregnant rats’ parameters (Mean ± SD)
Groups Maternal Wt. Placental Wt. Brain Wt.
Gain (gm) (gm) (gm)
Control (n=8) 96.6 ± 11.9 0.73 ± 0.011 1.74 ± 0.09
Cur (n=8) 100.1 ± 9.6 0.74 ± 0.031 1.75 ± 0.11
DMSO (n=8) 98.35 ± 10.75 0.735 ± 0.021 1.745 ± 0.10
L160 (n=8) 80.6 ± 12.9 0.63 ± 0.014 1.59 ± 0.07
P1
<0.05 P1
<0.001 P1
<0.05
P2
<0.01 P2
<0.001 P2
<0.01
P3
<0.05 P3
<0.001 P3
<0.05
L160 + Cur (n=8) 95.7 ± 7.83 0.68 ± 0.019 1.729 ± 0.04
P4
<0.05 P4
<0.001 P4
<0.05
L320 (n=6) 75.0 ± 6.93 0.58 ± 0.018 1.56 ± 0.12
P1
<0.001 P1
<0.001 P1
<0.01
P2
<0.001 P2
<0.001 P2
<0.001
P3
<0.001 P3
<0.001 P3
<0.01
L320 + Cur (n=8) 90.1 ± 7.12 0.64 ± 0.028 1.699 ± 0.05
P5
<0.05 P5
<0.001 P5
<0.05
F value 7.668 67.733 6.545
Number of rat per treatment group = 8 except for the high lead dose. ANOVA test with
Bonferroni post hoc test:
P1
: compared to control group. P2
: compared to Cur group. P3
: compared to DMSO group. P4
:
compared to L160 group. P5
: compared to L320 group.
of MDA levels in the fetal brains of Pb-treated
groups, which was significant when compared
to the control group; this was higher in the group
that received the larger Pb dose. Also, there was
a decrease of SOD, CAT, and GPx levels in
Pb-treated groups, which was significant when
compared to the control group; these levels were
lower in the group given the higher Pb dose. In
contrast, co-administration of Cur along with Pb
resulted again in the decrease of MDA and the
increase of antioxidant enzyme activities.
Histological results
Examination of the H&E-stained sections
of the cerebral cortex of the mother rats showed
that there were nearly the same findings in the
control, Cur, and DMSO-treated mother groups.
In general, normal histoarchitecture was seen in
the six layers of the cerebral cortex (Fig. 1 A, B
& C). In the Pb-treated groups, the examination
revealed variable degrees of histopathological
changes, which were less evident in the lower
dose groups (Fig. 2 A & B) than in the higher dose
groups (Fig. 3 A & B). Disorganization and lack
of characteristic, typical, layered structures were
seen with some vacuoles of variable sizes between
cells. Some pyramidal cells appeared irregular
in shape and darkly stained with loss of their
processes; others showed marked vacuolization
with faintly stained cytoplasm. Most of granular
cells were affected and became ill-defined and
faintly stained with pericellular halos. Also, some
apoptotic cells with dense nuclei were observed.
Regarding the Pb and Cur treated groups (Fig. 4
A, B & C), the examination showed improvement
of histological appearance of the cortical layers,
which appeared similar to the control group with
decreased cellular damage, especially with the
low Pb-dose group. The pyramidal cells appeared
almost normal with vesicular nuclei; a few were
still vacuolated with faintly stained acidophilic
cytoplasm.The immunohistochemical examination
of GFAP-stained sections of the cerebral cortex
from the above groups revealed a few GFAP-
positive immuno-reactive astrocytes with their
processes dispersed in between different cell
layers of the cerebral cortex in the control, Cur,
and DMSO-treated groups (Fig. 1 D). In the Pb-
treated groups, an apparent increase in the number
9. 879 Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
Table 3. Effect of gestational Pb and Cur co-administration on
materno-fetal Pb concentrations (Mean ± SD)
Groups Maternal blood Maternal Groups Fetal brain
(N of each) Pb level (µg/dl) brain Pb level (N of each) Pb level
(µg/gm) (µg/gm)
Control (N=8) 5.3 ± 0.99 0.06 ± 0.004 Control (N=102) 0.010 ± 0.003
Cur (N=8) 5.1 ± 1.21 0.05 ± 0.011 Cur (N=98) 0.008 ± 0.002
DMSO (N=8) 5.2 ± 1.1 0.055 ± 0.0075 DMSO (N=102) 0.009 ± 0.0025
L160 (N=8) 23.7 ± 4.19 1.05 ± 0.13 L160 (N=83) 0.43 ± 0.011
P1
<0.001 P1
<0.001 P1
<0.001
P2
<0.001 P2
<0.001 P2
<0.001
P3
<0.001 P3
<0.001 P3
<0.001
L160 + Cur (N=8) 10.1 ± 4.45 0.29 ± 0.17 L160 + Cur (N=92) 0.06 ± 0.009
P4
<0.001 P4
<0.001 P4
<0.001
L320 (N=6) 42.5 ± 5.41 1.60 ± 0.32 L320 (N=79) 0.85 ± 0.17
P1
<0.001 P1
<0.001 P1
<0.001
P2
<0.001 P2
<0.001 P2
<0.001
P3
<0.001 P3
<0.001 P3
<0.001
L320 + Cur (N=8) 15.2 ± 3.24 0.33 ± 0.12 L320 + Cur (N=88) 0.23 ± 0.07
P5
<0.001 P5
<0.001 P5
<0.001
F value 132.12 124.93 F value 1992.1
Number of rat per treatment group = 8 except for the high lead dose. ANOVA test with Bonferroni post hoc test. P1
:
compared to control group. P2
: compared to Cur group. P3
: compared to DMSO group. P4
: compared to L160 group.
P5
: compared to L320 group
Table 4. Effect of gestational Pb and Cur administration on the lipid
peroxidation and antioxidant enzyme activities of the maternal brains (Mean ± SD)
Groups MDA SOD CAT GPx
(nmol/ gm tissue) (U/gm Tissue) (µmole/ gm Tissue) (µmol/ gm tissue)
Control (n=8) 17.43± 0.10 69.11± 9.21 250.1 ± 4.1 22.3 ± 1.1
Cur (n=8) 15.88± 0.14 68.18± 6.22 243.1 ± 7.3 21.7 ± 2.7
DMSO (n=8) 16.66± 0.12 68.65± 7.72 246.6 ± 5.7 22 ± 1.9
L160 (n=8) 29.42 ± 0.86 51.32 ± 3.41 217.3 ± 6.3 17.4 ± 2.4
P1
<0.001 P1
<0.001 P1
<0.001 P1
<0.01
P2
<0.001 P2
<0.001 P2
<0.001 P2
<0.01
P3
<0.001 P3
<0.001 P3
<0.001 P3
<0.01
L160 + Cur (n=8) 19.94 ± 0.92 63.27 ± 2.16 236.4 ± 5.9 21.1 ± 1.9
P4
<0.001 P4
<0.001 P4
<0.001 P4
<0.001
L320 (n=6) 46.38 ± 1.27 41.56 ± 4.01 197.4 ± 7.1 12.6 ± 1.8
P1
<0.001 P1
<0.001 P1
<0.001 P1
<0.001
P2
<0.001 P2
<0.001 P2
<0.001 P2
<0.001
P3
<0.001 P3
<0.001 P3
<0.001 P3
<0.001
L320 + Cur (n=8) 23.74 ± 0.96 59.42 ± 3.17 218.1 ± 7.2 19.8 ± 3.3
P5
<0.001 P5
<0.001 P5
<0.001 P5
<0.001
F value 1590 26.933 75.433 19.284
Number of rat per treatment group = 8 except for the high lead dose. ANOVA test with Bonferroni post hoc test:
P1
: compared to control group. P2
: compared to Cur group. P3
: compared to DMSO group. P4
: compared to L160 group.
P5
: compared to L320 group.
10. 880Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
Table 5. Effect of gestational Pb and Cur administration on the lipid peroxidation
and antioxidant enzyme activities of the fetal brains (Mean ± SD)
Groups (N of each) MDA SOD CAT GPx
(nmol/ gm tissue) (U/gm Tissue) (µmole/ gm Tissue) (µmol/ gm tissue)
Control (n=102) 6.33 ± 1.9 0.63 ± 0.18 16.6 ± 4.1 15.2 ± 2.8
Cur (n=98) 5.88 ± 1.6 0.62 ± 0.12 15.9 ± 2.3 17.1 ± 2.3
DMSO (n=102) 6.1 ± 1.75 0.625 ± 0.15 16.25 ± 3.2 16.15 ± 2.55
L160 (n=83) 11.12 ± 2.1 0.51 ± 0.19 23.1 ± 6.3 11.4 ± 2.6
P1
<0.001 P1
<0.001 P1
<0.001 P1
<0.001
P2
<0.001 P2
<0.001 P2
<0.001 P2
<0.001
P3
<0.001 P3
<0.001 P3
<0.001 P3
<0.001
L160 + Cur (n=92) 7.92 ± 1.8 0.60 ± 0.16 19.2 ± 6.1 13.1 ± 2.9
P4
<0.001 P4
<0.01 P4
<0.001 P4
<0.001
L320 (n=79) 22.47 ± 4.7 0.38 ± 0.17 35.4 ± 7.3 8.8 ± 2.7
P1
<0.001 P1
<0.001 P1
<0.001 P1
<0.001
P2
<0.001 P2
<0.001 P2
<0.001 P2
<0.001
P3
<0.001 P3
<0.001 P3
<0.001 P3
<0.001
L320 + Cur (n=88) 9.53 ± 1.7 0.54 ± 0.15 22.4 ± 6.8 10.7 ± 3.1
P5
<0.001 P5
<0.001 P5
<0.001 P5
<0.001
F value 514.68 27.228 141.05 115.44
ANOVA test with Bonferroni post hoc test: P1
: compared to control group. P2
: compared to Cur group. P3
: compared to
DMSO group. P4
: compared to L160 group. P5
: compared to L320 group
Table 6. Area percentage of GFAP (Mean ± SD)
Groups (N of each) Maternal GFAP Groups Fetal GFAP
area percentage (N of each) area percentage
Control (n=8) 0.563 ± 0.188 Control (n=102) 0.285 ± 0.026
Cur (n=8) 0.55 ± 0.175 Cur (n=98) 0.275 ± 0.086
DMSO (n=8) 0.57 ± 0.19 DMSO (n=102) 0.280 ± 0.095
L160 (n=8) 1.1 ± 0.37 L160 (n=83) 0.55 ± 0.185
P1
<0.01 P1
<0.001
P2
<0.01 P2
<0.001
P3
<0.01 P3
<0.001
L160 + Cur (n=8) 0.602 ± 0.209 L160 + Cur (n=92) 0.301 ± 0.105
P4
<0.05 P4
<0.001
L320 (n=6) 1.42 ± 0.473 L320 (n=79) 0.71 ± 0.237
P1
<0.001 P1
<0.001
P2
<0.001 P2
<0.001
P3
<0.001 P3
<0.001
L320 + Cur (n=8) 0.600 ± 0.2 L320 + Cur (n=88) 0.32 ± 0.11
P5
<0.001 P5
<0.001
F value 12.289 F value 147.08
of GFAPimmuno-reactive astrocytes was observed
as compared to the control animals, which was
more rigorous in the group that received the high
dose of Pb (Fig. 3 C) than that which received the
low dose (Fig. 2 C). In the Pb- and Cur-treated
group (Fig. 4 D), a noticeable decrease in the GFAP
immune-reactive astrocytes was seen as compared
to the Pb-treated rats (Table 6).
Examination of the H&E-stained sections
from the fetal brains belonging to the control, Cur,
and DMSO-treated groups showed nearly the same,
normal histological findings, which displayed
11. 881 Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
Fig. 4. Photomicrographs of cerebral cortex from Pb and Cur-treated mother rats showing: A) an improvement in
the histoarchitecture with organized layers. B) more or less normal pyramidal cells (P) and granular cells (G). C) a
decrease in the GFAP immunoreactive astrocytes as compared Pb-treated rats (↑). pm= pia matter, bv= blood vessel.
[A: H&E X100 & B: 400, C: GFAP X 200]
normal appearance of the telencephalon (which
appeared with distinct structure and was formed of
five zones) with its lateral ventricle (Fig. 5A& B).
In the low-dose Pb-treated group, the picture was
similar with no difference from that of the control
group. In the high-dose Pb-treated group (Fig. 6A&
B), the examination of fetal brains revealed variable
degrees of histopathological changes where there
was a less degree of maturation than of the control
fetuses in the form of dilation of the lateral ventricle
as well as thinning and hardly distinguishable
arrangement of the telencephalic wall layers.
Also, thinned ventricular and subventricular zones,
widening of the intermediate zone, hypoplasia, and
reduction of the cortical zone were seen. While in
the fetal brains from the Pb- and Cur-treated group
(Fig. 7A& B), the examination showed regressive
changes, and the picture was similar to that of
the control group regarding the thickness of the
telencephalic wall and size of the lateral ventricle.
The immunohistochemical examination of GFAP-
stained sections of the fetal brain showed negative
or very little GFAP-positive cellular reaction in the
superficial layers of the telencephalic wall (Fig. 5
C). In the fetal brains from the high-dose Pb-treated
group, there was apparent increase in the number of
GFAP immuno-reactive astrocytes as compared to
the control group (Fig. 6 C). However, in the fetal
brain from Pb- and Cur-treated group, a reduction
of GFAPimmuno-reactive astrocytes was observed
(Table 6, Fig. 7 C).
DISCUSSION
In the current study, Pb at a dose of 160
and 320 mg/kg b.wt. during pregnancy caused a
significant reduction in brain weight, body weight
and fetal body weight when compared to the
control rats, which was obvious in those received
the larger dose of Pb. In accordance with these
findings, the authors reported that Pb causes several
adverse health effects that are dose-dependent and
somewhat irreversible 46
.Also, it was found that Pb
induces an important reduction in pups’ body and
brain weight at postnatal days 0-21 when their dams
consumed drinking-water containing 300 mg/L of
Pb 12, 47
.
The central nervous system is considered
to be the primary target of Pb exposure, especially
in the developing brain, leading to weakening of
12. 882 Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
Fig. 5. Photomicrographs of the fetal brain at GD20 from
control and Cur treated groups showing:A) telencephalic
wall (TW), which is formed of five basic zones: marginal
zone (MZ), cortical zone (CZ), intermediate zone (IZ),
subventricular zone (SZ) and ventricular zone (VZ). B)
negative or very few and weak GFAP positive cellular
reaction (↑), which are scattered in the superficial layers
of the telencephlic wall. LV = lateral ventricle [A: H&E
X 200, B: GFAP X 200].
Fig. 6. Photomicrographs of the fetal brain at GD20
from high dose Pb-treated group showing A) a hardly
distinguishable arrangement of the telencephalic wall
layers, with thinned ventricular (VZ) and subventricular
(SZ) zones and widening of the intermediate zone (IZ),
hypoplasia and reduction of the cortical zone (CZ) and
disruption of the marginal zone (MZ). B) a presence of
GFAP positive reaction (↑), which was more scattered
in the superficial layers of the telencephalic wall. LV =
lateral ventricle [A: H&E X 200, B: GFAP X 200]
Fig. 7. Photomicrographs of the fetal brain at GD20
from high dose Pb and Cur treated group showing: A)
a distinguishable arrangement of the telencephalic wall
layers, which appeared similar to the control fetal brain.
B) a reduction in the number of GFAP immunoreactive
astrocytes (↑).LV = lateral ventricle [A: H&E X 200,
B: GFAP X 200]
cognitive abilities and interruption of behavioral
development and attentiveness in children 48
. These
results could be explained by the fact that infants
absorb 50% of Pb that are exposed to, whereas
adults absorb 10% 11, 23, 49
. Also, Pb traverses the
blood-brain barrier simply while the brain is
developing in a rapid growth and an intense cellular
proliferation. This is due to blood-brain barrier
immaturity, which caused absorption of Pb 11, 23, 49
.
Studies have revealed that the fetuses of pregnant
mothers predisposed to Pb level (0.01% and 0.05%
w/v orally for 45 days) exhibited higher fetal brain
Pb levels 50
.
The elevated maternal blood Pb level in
the current results that is obvious in the group with
a higher dose of Pb, shows a correlation between
maternal and umbilical cord blood Pb levels. Those
findings support the concept that Pb might easily
cross to the placenta in a dose-responsive manner.
It was described that the placenta can’t protect the
fetus from exposure to Pb, because it is able to cross
the placental barrier freely 51
. Current results come
in the same line with other studies that compared
the Pb levels of umbilical cord blood and maternal
blood and with studies that declared that the Pb in
13. 883Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
new-born infants’blood was a reflection of that of
the mother 52
.
Current results indicated that the dam’s Pb
exposure caused an increase of Pb in fetus blood
and placenta, in additon to elevation of the Pb in the
brain of the developing fetus. Similarly, preceding
studies showed that Pb was highly concentrated
in the placenta, umbilical cord and brain, and it is
supposed that the placenta and umbilical cord might
be respectable biomarkers of fetal Pb exposure 53
.
Furthermore, studies have demonstrated that Pb
infiltrate the immature blood-brain barrier and
accumulate in the developing brain, which seems
to be vulnerable to metal infiltration; this results in
a significant dose-dependent rise, confirming the
transplacental metal passage from the mothers 6
.
In the current work, it was found that Pb
causes a significant increase in LPO, as evidenced
by the high MDA level in the maternal and fetal
brains; this was accompanied by marked reduction
of antioxidant enzymes (SOD, CAT, and GPx) in
different Pb exposure groups. It was stated that Pb-
induced disturbance of the prooxidant/antioxidant
balance in the brain might encourage impairment
to different cellular components, including nucleic
acids, membrane lipids, and proteins 54
. Also, it
was shown that MDA level is strongly correlated
with Pb concentration in the brains of exposed rats
55
. Moreover, these results were consistent with
earlier animal and human studies, which suggested
that exposure to Pb was associated with increased
oxidative stress and occurrence of neurotoxicity
due to oxidative damages, as the brain consumes
20% of the body’s oxygen 56
.
The results also showed increased LPO in
the fetal brains with pre-natal Pb exposure. It was
declared that the toxic effects of Pb on the fetal
brain are undoubtedly the main significant and
meticulously studied consequence of intrauterine
Pb exposure. This injurious effect of high Pb levels
has been well-recognized 57,58
. Such effects might
be affecting the morphological developments and
the sensory reflexes of the pups as well as the
behavior of young adult offspring59
.
Histolopathologically, the present study
displayed a variable degree of structural impairment
of the maternal and fetal brains in the Pb-treated
groups, which were more understandable in those
exposed to the higher dose of Pb. It was stated
previously that Pb-induced damage occurred
primarily in the cerebrum, hippocampus and
cerebellum affecting various biological activities
at the molecular, cellular, and intracellular levels,
which can cause morphological modifications in
the brain that may persist even after Pb levels have
dropped 60
. In this study, there were decreased
pyramidal cells along with the presence of
degenerated cells with pyknotic nuclei in Pb-treated
groups in comparison to control. This agreed with
studies that accredited these findings to the direct
effect of Pb on brain cells 61
. Correspondingly,
Pb-induced cell death has been established in the
cortex and cerebellum on neonatal rats in-vivo
(2-4 weeks old). This indicates a sophisticated
sensitivity in younger rats with apoptotic cells 49
.
The study showed that fetal brains
from Pb-exposed groups displayed reduced
differentiation and cell apoptosis degeneration.
Accordingly, it was noticed that the intrauterine
exposure to Pb is harmfully disturbs cellular
proliferation, differentiation and synaptic growth
of the brain, which causes mental retardation or
movement disorders 62
. Accordingly, studies have
described that Pb exposure during embryonic
development causes cortical and cerebellar
impairment in newborn and in the developing
hippocampus. These effects happen cause of Pb
interferes with several proliferative and apoptotic
pathways 63
.
In the current study, the effect of Pb on
the astrocytes was observed using immunolabeling.
Increased GFAP-positive astrocytes were found
in the Pb treated maternal brains; this increase or
gliosis is explained as hyper-reactivity of astrocytes
that attempt to provide accommodation against the
toxic effect of Pb, thus protecting neurons from its
hazardous effects 61
. The mechanism that explain
the increased of GFAP-positive astrocytes and
GFAP content in the neonatal brain after maternal
Pb intake detected in the current study might be
attributed to a potential role of cytokines, which
play an important part in modulating astrogliosis.
Moreover, it was described that the observed
gliosis in the Pb-treated group might be caused by
the formation of ROS and reduced antioxidants
42
. Similarly, studies have observed an elevated
GFAP in numerous regions of the brain after Pb
exposure, mainly in the hippocampus and the
cerebellar cortex. Consequently, the detection
of GFAP expression might probably be an
14. 884 Saleh et al., Biomed. & Pharmacol. J, Vol. 11(2), 871-887 (2018)
appropriate marker to determine neurodegenerative
impairments 64
. Regarding the fetal brains at GD20,
few GFAP-positive astrocytes were occasionally
seen. GFAP-positive astrocytes were detected in
the cortex of the brain in the examined groups.
Focally accumulated GFAP-positive astrocytes in
the cortex were apparent in brains from the Pb-
treated group.
Co-administration of Cur together with
Pb to the mother rats produced a significant
improvement, as evidenced by the study parameters
and the histopathological findings in maternal
and fetal brains, which appeared like the control
rats, especially in the group that received the
smaller dose of Pb. Similarly, it has been reported
that Cur has great potential for the prevention
of multiple neurological conditions 65
. Also,
several studies have shown that Cur exhibits
protective effects against oxidative damage by
exerting a potent scavenging effect for ROS and
increased intracellular glutathione concentration
66
. Moreover, some animal studies have shown
that administration of Cur after brain ischemia has
protective effects and significantly diminishes lipid
peroxidation, mitochondrial dysfunction, and glial
activation, as well as infarct volume; moreover, it
improves cognitive deficits, neurological scores,
and locomotor activity 51
.
Furthermore, the protective role of the
antioxidant Cur is proved by a reduced MDA
concentration in the brain due to Pb-caused
oxidative stress 67
. Suppression of SOD activity by
Pb was shown in an in-vitro experiment that support
the concept that Pb can cause reduced scavenging
of ROS, which results in oxidative impairment.
SOD activity is a significant constituent of the
cellular antioxidant system that defends cells from
the destructive effects of oxidants 68
. Cur showed a
neuroprotective effect in the different regions of the
brain 69
. Cur is thought to exert its anti-apoptotic and
neuroprotective actions in multiple ways, including
as a strong anti-inflammatory and antioxidant, and
through neuromodulating activities 70
.Also, it was
shown that Cur exhibits a great capacity to defend
brain lipids from peroxidation, improve SOD
activity and shows the important inhibitory action
against H2
O2
-caused cell injury 68, 71
.
Conclusion
This study is important in providing
evidence of the beneficial role of Cur as a natural
antioxidant in the protection against maternal and
fetal Pb neurotoxicity. Finally, efforts with active
steps should be taken towards the prevention of
occupational exposure to this metal.
Acknowledgements
This project was funded by the Deanship
of Scientific Research (DSR), King Abdulaziz
University, Jeddah, under grant No. (RG/04/32).
The authors, therefore, acknowledge with thanks
DSR technical and financial support.
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