This research article studied the effects of quercetin (QCT) on experimentally induced diabetes in rats. Rats were divided into three groups: a control group, a diabetic group induced with streptozotocin (STZ), and a QCT-treated group that received QCT before and after STZ induction. Blood glucose levels increased significantly in the diabetic group but decreased in the QCT-treated group. Histological analysis found that STZ caused pancreatic beta cell degeneration and inflammation in the diabetic group. QCT treatment reversed many of these changes in the pancreas and increased beta cell numbers. Immunohistochemistry revealed that STZ increased iNOS and caspase-3, markers of inflammation and apoptosis, while QCT
Evaluation of hepatoprotective agents - Hemant KanaseHemant Kanase
1. Introduction
2. Hepatotoxicity: Mechanism
3. Therapeutic strategies available – their limitations
4. In vivo models of liver damage
- Non-invasive model
a. Chemically induced hepatotoxicity
b. Drug-induced hepatotoxicity
c. Radiation-induced hepatotoxicity
d. Metal-induced hepatotoxicity
e. Diet-induced hepatotoxicity
Models of Acute Hepatitis
Models of chronic hepatitis
Models of fibrosis
Models of cholestasis
Models of steatosis
4. Problems faced with animal studies
5. In vitro models of liver damage
6. Advantages and disadvantages of in vitro models
7. Parameters of evaluation
8. Clinical Assessment
Hepatoprotective Activity of Methanolic Extract of Whole Plant of Pulicaria W...IOSRJPBS
Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for liver injury. The present study was conducted to evaluate the hepatoprotective activity of methanolic extract of whole plant of Pulicaria wightiana in wistar rats. The studies were conducted using the two popular inducing agents Paracetamol (2 g/kg, p.o.) in 1% NaCMC and Carbon tetrachloride (1 ml/kg). Silymarin (100 mg/kg, p.o.) was used as reference drug in the respective models. The effect was estimated by measuring the enzymatic levels and histo- pathological studies. The methanolic extract of whole plant of Pulicaria wightiana has shown very significant hepatoprotection against both Paracetamol and CCl4 - induced hepatotoxicity study models in wistar rats. This was evidenced by marked reduction in marker enzymes in serum. Histopathological studies also confirmed the hepatoprotective nature of the extract
Evaluation of hepatoprotective agents - Hemant KanaseHemant Kanase
1. Introduction
2. Hepatotoxicity: Mechanism
3. Therapeutic strategies available – their limitations
4. In vivo models of liver damage
- Non-invasive model
a. Chemically induced hepatotoxicity
b. Drug-induced hepatotoxicity
c. Radiation-induced hepatotoxicity
d. Metal-induced hepatotoxicity
e. Diet-induced hepatotoxicity
Models of Acute Hepatitis
Models of chronic hepatitis
Models of fibrosis
Models of cholestasis
Models of steatosis
4. Problems faced with animal studies
5. In vitro models of liver damage
6. Advantages and disadvantages of in vitro models
7. Parameters of evaluation
8. Clinical Assessment
Hepatoprotective Activity of Methanolic Extract of Whole Plant of Pulicaria W...IOSRJPBS
Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for liver injury. The present study was conducted to evaluate the hepatoprotective activity of methanolic extract of whole plant of Pulicaria wightiana in wistar rats. The studies were conducted using the two popular inducing agents Paracetamol (2 g/kg, p.o.) in 1% NaCMC and Carbon tetrachloride (1 ml/kg). Silymarin (100 mg/kg, p.o.) was used as reference drug in the respective models. The effect was estimated by measuring the enzymatic levels and histo- pathological studies. The methanolic extract of whole plant of Pulicaria wightiana has shown very significant hepatoprotection against both Paracetamol and CCl4 - induced hepatotoxicity study models in wistar rats. This was evidenced by marked reduction in marker enzymes in serum. Histopathological studies also confirmed the hepatoprotective nature of the extract
Diabetes mellitus: The Pandemic of 21st Century!RahulGupta2015
Diabetes mellitus is a major global metabolic disorder of 21 st century. This is due to its broad spectrum of associated complications with risks, like cardiac and renal disorders. The rapid growth of diabetes is becoming a major burden upon healthcare facilities in all affected countries. Due to lack of definitive preventative measures of diabetes, we must be aware of this pandemic and follow a disciplined lifestyle to limit it. In this communication, recent advances in diabetes management and current preventative measures have been concluded.
Pharmacodynamic study of Jerusalem artichoke particles in type I and II diabe...Premier Publishers
To study the therapeutic effect of Jerusalem artichoke particles in type I and type II diabetic rats. Male Sprague–Dawley (SD) rats were intraperitoneally injected with 30 mg/kg streptozotocin (STZ) for 3 consecutive days to generate a type I diabetic rat model. The rats were orally administered Jerusalem artichoke particles (50, 100, or 150 mg/kg) once a day for 3 consecutive weeks. Fasting blood glucose levels were determined by ELISA. Male SD rats were fed a high-fat and high-sugar diet then received an intraperitoneal injection of 35 mg/kg STZ to generate a type II diabetic rat model. The rats were treated as mentioned above for 4 consecutive weeks. Fasting blood glucose levels were determined using the glucose oxidase method. Jerusalem artichoke particles significantly reduced blood glucose concentrations in type I and type II diabetic rats. Following 50, 100 and 150 mg/kg Jerusalem artichoke particles treatment for specified weeks, blood glucose concentrations were decreased by 9.7%, 21.69% and 15.48% in type I diabetic rats, respectively; and type II diabetic rats were decreased by 12.07%, 28.57% and 21.80%, respectively. Jerusalem artichoke particles have a hypoglycemic effect in type I and type II diabetic rats.
ABSTRACT- Previous studies have suggested an association between vegetarian persons and non-vegetarian persons, although this relationship
positive correlation significant. The present study was designed to investigate comparative study of lipid profile levels in vegetarian and nonvegetarian
person. The lipid profile is used to determine the risk of obesity, heart disease in myocardial infarction, atherosclerosis and help in deciding
treatment has borderline or high risk. the present study was undertaken to compare case and control produce effect on individuals lipid profile, the
parameters of lipid metabolism i.e. cholesterol, tri-glyceride, high density lipoprotein, low density lipoprotein of the age of 20-85 years and early
aged 50 years and above males and females, divided categories i.e. vegetarian and non- vegetarian persons. the study was done on 20 cases in 10
control (non-vegetarians) and 10 cases (vegetarians) diet was significantly found to reduce the values of all the parameter lipid metabolism except
HDL-Cholesterol(45.02± 9.595; p<0.0001).when><0.0001 ) from this study, it can be concluded
that along with diet, sex and age factor also influence parameters of lipid metabolism.
Key words- Vegetarian persons, non-Vegetarian, Lipid profile
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is an open access international journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
µCT analysis reveals that Cissus quadrangularis L. Stem and Trigonella foenum...RahulGupta2015
Cissus quadrangularis L. (hadjod) and Trigonella foenum-graecum L. (fenugreek) plant parts are used for fracture healing and as an antidiabetic agent, respectively in traditional medicine. This study aimed to investigate the efficacy of C. quadrangularis stem bark extract (CQ) and T. foenum-graecum seed extract (TFG) therapy for the treatment of type I diabetes induced osteopenia. Alloxan (dissolved in 0.1 M citrate buffer (pH = 4.5); intraperitoneally injected @ 130 mg/kg body weight) induced type I diabetic rats were treated with individual and combined doses of ethanol extracts of CQ and TFG for consecutive 30 days @ 250 and 500 mg per kg body weight, orally. Insulin (0.5 IU/kg body weight) was chosen as standard. Body weight and fasting blood glucose were recorded. Two-dimensional (2D) and three-dimensional (3D) analysis of the femur and tibia were performed using micro-computed tomography (µCT) scan to measure histomorphometric parameters of trabecular and cortical regions and bone mineral density (BMD). Elevated level of fasting blood glucose was restored to the vehicle-treated group after treatment with CQ and TFG. Both the extracts significantly improved trabecular histomorphometric parameters, viz. BMD, percent bone volume, trabecular number, trabecular separation, connection density. Cortical mean total cross-sectional bone area, cross-sectional thickness, mean total cross-sectional tissue area were comparable to the vehicle-treated group. CQ and TFG combination therapy showed a marked improvement in bone microarchitecture and can be given together as a potential alternative medicine to insulin for prevention of type I diabetes induced osteopathy. Therefore, it can be considered in the management of diabetic osteopathy in humans.
Iris Publishers - journals of biostatistics | Biomathematical Analysis of the...IrisPublishers
Liver fibrosis is the final common stage of the most chronic liver diseases, it is caused by several factors which lead to a major worldwide health care burden. Over the decades, the understanding of the liver fibrosis disease was growing rapidly, several studies reported that this progress could be regressed or reversed, which give us a bright prospect in developing anti-fibrotic therapies.In this experiment, liver fibrosis was fully developed after CCl4 induction for 7 weeks in eight animals. Clinical pathologic parameters, four indicators of hepatic fibrosis in monkey showed similarly changes in human. All animals had liver fibrosis after 1.5 months of CCl4 induction, and liver fibrosis still existed after 9 months recovery periods, the fibrosis stages in most animals had no obvious regression without treatment. Biomathematical analysis of the liver fibrosis would aid to utilize the anti-fibrotic therapies and their derivatives for various biomedical applications.
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.
Hepatoprotective Effect of Aqueous Extracts of Some Medicinal Plant Mixtures ...IOSRJPBS
The rhizomes of Ginger (Zingiberofficinale), Turmeric (Curcuma longa), Licorice (Glycyrrhizaglabra), the bark of Cinnamon tree,(Cinnamomumzeylanicum) and the calyces of red Roselle (Hibiscus sabdariffa L.)are herbs used in thishepatoprotective studies. This study evaluates the hepatoprotective activity of water extract mixtures using carbon tetrachloride (CCl4)-induced liver injury in rats.In vitroantioxidant activity of plant water extracts was determined using DPPH. The water extractmixtures wereadministered for 10 days; on the 10thday all rats were challenged with CCl4 except control group animals. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin levels were determined to prove the hepatoprotectiveeffect.The enzyme activities were significantly increased in CCl4 treated rats. The four water extract mixtures exhibited significant (P<0.05)><0.05) increased in all the water extract mixtures used.
In vivo studies are those in which the effects of various biological activities are tested on whole, living organisms or cells, usually, including humans, and animals, as opposed to a tissue extract or dead organism. Animal testing and clinical trials are major elements of in vivo research.
Diabetes mellitus: The Pandemic of 21st Century!RahulGupta2015
Diabetes mellitus is a major global metabolic disorder of 21 st century. This is due to its broad spectrum of associated complications with risks, like cardiac and renal disorders. The rapid growth of diabetes is becoming a major burden upon healthcare facilities in all affected countries. Due to lack of definitive preventative measures of diabetes, we must be aware of this pandemic and follow a disciplined lifestyle to limit it. In this communication, recent advances in diabetes management and current preventative measures have been concluded.
Pharmacodynamic study of Jerusalem artichoke particles in type I and II diabe...Premier Publishers
To study the therapeutic effect of Jerusalem artichoke particles in type I and type II diabetic rats. Male Sprague–Dawley (SD) rats were intraperitoneally injected with 30 mg/kg streptozotocin (STZ) for 3 consecutive days to generate a type I diabetic rat model. The rats were orally administered Jerusalem artichoke particles (50, 100, or 150 mg/kg) once a day for 3 consecutive weeks. Fasting blood glucose levels were determined by ELISA. Male SD rats were fed a high-fat and high-sugar diet then received an intraperitoneal injection of 35 mg/kg STZ to generate a type II diabetic rat model. The rats were treated as mentioned above for 4 consecutive weeks. Fasting blood glucose levels were determined using the glucose oxidase method. Jerusalem artichoke particles significantly reduced blood glucose concentrations in type I and type II diabetic rats. Following 50, 100 and 150 mg/kg Jerusalem artichoke particles treatment for specified weeks, blood glucose concentrations were decreased by 9.7%, 21.69% and 15.48% in type I diabetic rats, respectively; and type II diabetic rats were decreased by 12.07%, 28.57% and 21.80%, respectively. Jerusalem artichoke particles have a hypoglycemic effect in type I and type II diabetic rats.
ABSTRACT- Previous studies have suggested an association between vegetarian persons and non-vegetarian persons, although this relationship
positive correlation significant. The present study was designed to investigate comparative study of lipid profile levels in vegetarian and nonvegetarian
person. The lipid profile is used to determine the risk of obesity, heart disease in myocardial infarction, atherosclerosis and help in deciding
treatment has borderline or high risk. the present study was undertaken to compare case and control produce effect on individuals lipid profile, the
parameters of lipid metabolism i.e. cholesterol, tri-glyceride, high density lipoprotein, low density lipoprotein of the age of 20-85 years and early
aged 50 years and above males and females, divided categories i.e. vegetarian and non- vegetarian persons. the study was done on 20 cases in 10
control (non-vegetarians) and 10 cases (vegetarians) diet was significantly found to reduce the values of all the parameter lipid metabolism except
HDL-Cholesterol(45.02± 9.595; p<0.0001).when><0.0001 ) from this study, it can be concluded
that along with diet, sex and age factor also influence parameters of lipid metabolism.
Key words- Vegetarian persons, non-Vegetarian, Lipid profile
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is an open access international journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
µCT analysis reveals that Cissus quadrangularis L. Stem and Trigonella foenum...RahulGupta2015
Cissus quadrangularis L. (hadjod) and Trigonella foenum-graecum L. (fenugreek) plant parts are used for fracture healing and as an antidiabetic agent, respectively in traditional medicine. This study aimed to investigate the efficacy of C. quadrangularis stem bark extract (CQ) and T. foenum-graecum seed extract (TFG) therapy for the treatment of type I diabetes induced osteopenia. Alloxan (dissolved in 0.1 M citrate buffer (pH = 4.5); intraperitoneally injected @ 130 mg/kg body weight) induced type I diabetic rats were treated with individual and combined doses of ethanol extracts of CQ and TFG for consecutive 30 days @ 250 and 500 mg per kg body weight, orally. Insulin (0.5 IU/kg body weight) was chosen as standard. Body weight and fasting blood glucose were recorded. Two-dimensional (2D) and three-dimensional (3D) analysis of the femur and tibia were performed using micro-computed tomography (µCT) scan to measure histomorphometric parameters of trabecular and cortical regions and bone mineral density (BMD). Elevated level of fasting blood glucose was restored to the vehicle-treated group after treatment with CQ and TFG. Both the extracts significantly improved trabecular histomorphometric parameters, viz. BMD, percent bone volume, trabecular number, trabecular separation, connection density. Cortical mean total cross-sectional bone area, cross-sectional thickness, mean total cross-sectional tissue area were comparable to the vehicle-treated group. CQ and TFG combination therapy showed a marked improvement in bone microarchitecture and can be given together as a potential alternative medicine to insulin for prevention of type I diabetes induced osteopathy. Therefore, it can be considered in the management of diabetic osteopathy in humans.
Iris Publishers - journals of biostatistics | Biomathematical Analysis of the...IrisPublishers
Liver fibrosis is the final common stage of the most chronic liver diseases, it is caused by several factors which lead to a major worldwide health care burden. Over the decades, the understanding of the liver fibrosis disease was growing rapidly, several studies reported that this progress could be regressed or reversed, which give us a bright prospect in developing anti-fibrotic therapies.In this experiment, liver fibrosis was fully developed after CCl4 induction for 7 weeks in eight animals. Clinical pathologic parameters, four indicators of hepatic fibrosis in monkey showed similarly changes in human. All animals had liver fibrosis after 1.5 months of CCl4 induction, and liver fibrosis still existed after 9 months recovery periods, the fibrosis stages in most animals had no obvious regression without treatment. Biomathematical analysis of the liver fibrosis would aid to utilize the anti-fibrotic therapies and their derivatives for various biomedical applications.
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.
Hepatoprotective Effect of Aqueous Extracts of Some Medicinal Plant Mixtures ...IOSRJPBS
The rhizomes of Ginger (Zingiberofficinale), Turmeric (Curcuma longa), Licorice (Glycyrrhizaglabra), the bark of Cinnamon tree,(Cinnamomumzeylanicum) and the calyces of red Roselle (Hibiscus sabdariffa L.)are herbs used in thishepatoprotective studies. This study evaluates the hepatoprotective activity of water extract mixtures using carbon tetrachloride (CCl4)-induced liver injury in rats.In vitroantioxidant activity of plant water extracts was determined using DPPH. The water extractmixtures wereadministered for 10 days; on the 10thday all rats were challenged with CCl4 except control group animals. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin levels were determined to prove the hepatoprotectiveeffect.The enzyme activities were significantly increased in CCl4 treated rats. The four water extract mixtures exhibited significant (P<0.05)><0.05) increased in all the water extract mixtures used.
In vivo studies are those in which the effects of various biological activities are tested on whole, living organisms or cells, usually, including humans, and animals, as opposed to a tissue extract or dead organism. Animal testing and clinical trials are major elements of in vivo research.
this is a ppt on histotechniques,, all techniques from receiving samples to block making to sectioning to staining are discusses in detail..useful for postgraduate pathology students and lab technicians
How to Make Awesome SlideShares: Tips & TricksSlideShare
Turbocharge your online presence with SlideShare. We provide the best tips and tricks for succeeding on SlideShare. Get ideas for what to upload, tips for designing your deck and more.
Antihyperlipidemic Activity of Torbangun Extract (Coleus amboinicus Lour) on ...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Low beneficial effects of short term antidiabetic diet treatment in streptozo...iosrphr_editor
Oxidative stress is currently suggested to play a role in the pathogenesis of Diabetes mellitus. The role of dietary management in diabetes mellitus is to provide a proper balance of total nutrients while meeting the special dietary needs of the patient. The present study was designated to evaluate the effect of special antidiabetic diet treatment upon oxidative stress parameters in the initial stages of the development of diabetes. Male Wistar strain rats were used as an experimental model, divided into five groups. A significant decrease in superoxide dismutase and total glutathione activities were observed in the liver of diabetic rats when compared with control animals. The plasma level of aminotransferases, creatine kinase, lactate dehydrogenase and urea were significantly increased after induction of diabetes, in all groups under treatment. In contrast, rats fed special diet food, have shown slight different, but not significant changes. The findings of the present study suggest that special diet formula useful for prevention of progressive hyperglycaemia in age induced diabetes in dogs, could not restore the imbalance of cellular defence mechanism provoked by streptozotocin.
Whey protein products and their combination with L-methionine prevent liver f...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethac...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Antihyperglycemic Effect of Aqueous Leaf Extract of Mimusops elengi against S...BRNSS Publication Hub
Objective: The present study was hypothesized to evaluate the antihyperglycemic effect of aqueous leaf extract of Mimusops elengi on streptozotocin (STZ)-induced diabetic animals. Materials and Methods: Antidiabetic activity of M. elengi leaf extract at a dosage of 250 mg/kg body weight was evaluated. Results: The activity levels of glucose, triglycerides, total cholesterol, and serum glutamic pyruvic transaminase were significantly elevated in STZ-induced diabetic animals when compared to that of normal animals. After supplemented with aqueous leaf extract of M. elengi, animals group recorded significant lower blood glucose level. Conclusion: The aqueous leaf extract of M. elengi has been potent antidiabetic effect in male albino rat.
Research on Diabetes and hepatotoxicity in wistar rat By Nitin Kale final 24...NitinKale46
Thyroid hormone is the hormone that’s mainly responsible for controlling the speed of your body’s metabolism. In infants, thyroid hormone is critical for brain development. Your thyroid, a small, butterfly-shaped gland located at the front of your neck under your skin, makes and releases thyroid hormone. It’s a part of your endocrine system.A naturally occurring coumarin called Scopoletin (SPl) has been found to have anti-inflammatory, anti-diabetic, anti-microbial, and anti-cancer characteristics. Scopoletin has been proposed to act through the antioxidant Nrf2 pathway, the pro-inflammatory NF-B pathway, the Stat-3 pathway, the hypoxia signalling pathway, the Wnt-ꞵ signalling pathway, the Notch signalling pathway, the autophagy pathway, the hypoxia signalling pathway, and other signalling pathways, depending on the cell type, organ, experimental model, and disease studied
Effect of aqueous extract of phaseolus vulgaris l. (red kidney beans) on allo...IJSIT Editor
Aqueous extract of Phaseolus Vulgaris L. (Red Kidney Beans) was investigated for its effects in
alloxan induced-diabetic rats. Twenty four albino rats were randomly allocated into four groups (A-D) of six
rats each such that group A (diabetes control) received 0.5 mL distilled water, group B (diabetes) received
400 mg/kg bwt of extract, group C (normal control) received 0.5 mL of distilled water while group D (normal)
received 400 mg/kg bwt of extract, all extract were orally administered once daily for 14 days. Diabetes was
induced in groups A&B by single interperitonial injection of 150 mg/kg alloxan monohydrate. Phytochemical
screening indicated the presence of alkaloids, balsam, flavonoids, saponins, tannins, cyanogenic glycosides,
terpenes and steroids. The hypoglyceamic potential of Phasoelus vulgaris L. was expressed in diabetes
treated rats. Blood glucose, total protein, albumin and cholesterol levels of the diabetes treated rats and
normal treated rats were not significantly (p>0.05) altered when compared with the control rats. However,
these values were significantly (p<0.05)><0.05)>0.05) effects on PCV and Hb in all groups when compared to the normal control. The study showed that
the aqueous extract of Phasoelus vulgaris L. leaves possess hypoglycaemic, antidiabetic properties and
ameliorating the high levels of marker enzymes observed in diabetes untreated rats.
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
The global prevalence of obesity is increasing rapidly and high dietary fat intake is major risk factor for the development of obesity. The present study was taken undertaken to evaluate the effect of Argyreia Nervosa Burn.F leaf ethanol extract on serum lipid profile in Wistar male albino rat fed with high fat diet and to compare it with a standard hyperlipidemic drug Sibutramine (10mg/kg). Fifty four health Wistar albino male rats were randomized in to 9 groups of 6 animals each. The groups were followed as follows Group I: Sham operated Normal (Normal Diet), Group II: Control (High fat diet), Group III: Sibutramine 10 mg/kg + HFD, Group IV: EEAN (100mg/kg) + HFD, Group V: EEAN (200mg/kg) +HFD, Group VI: EEAN
(400mg/kg) + HFD, Remaining groups have received different types of extracts at various doses. Lipid profile in serum with high triglyceride (TG) and cholesterol levels were significantly reduced by treatment of 0.5g/day A. nervosa. The A. nervosa markedly lowers the levels of serum cholesterol and VLDL. The present investigation shows that all triton induced rats
displayed hyperlipidemia as shown by their elevated levels of serum and liver cholesterol, triglyceride, PL, VLDL, LDL and the reduction in the HDL level. It can be concluded that 0.5g/day of A. nervosa treatment was effective in reduction of cholesterol, PL, TG, VLDL, LDL and HDL in a dose dependant manner.
Anti-diabetic potentials of Sorbaria tomentosa Lindl. Rehder: Phytochemistry ...RaktimavaDasSarkar
Original Artcle by Falak Naz, Muhammad Zahoor, Muhammad Ayaz, Muhammad Ashraf, Asif Nawaz, Amal Alotaibi.
Presentation prepared by Raktimava Das Sarkar
Effect of Piper crocatum Extract Against Weight Loss and Liver Enzyme Levels ...iosrphr_editor
Piper crocatum is one of Indonesian medicinal plant that contain flavonoids, tannins, alkaloids, and saponins. Aims of this study were to evaluate the effect of Piper crocatum aqueous extract against a decrease in body weight (BW) and the activity of enzymes involved in lipid metabolism (AMPK, ACC, FAS) in liver obese rats. This study used four groups of Sprague dawley rat (n = 6), including normal group (N), obese controls (OC), Piper crocatum extract dose 1260 mg/kgBW (PcA), and Piper crocatum extract dose of 1890 mg/kgBW (PcB). Measurement of metabolic liver enzyme levels (AMPK, ACC, FAS) are using ELISA kit (CusabioTM). Results of this study showed that the PcA group produce the highest reduction in body weight (4.52%), and the lowest levels of ACC (9.13 ng/g) and FAS (360.68 ng/g) which was significantly different from obese control group (95% CI). Piper crocatum extract can't activate AMPK. The highest levels in rat liver AMPK is in N group with 8.42 ng/g, but this value is not significantly different from other groups.
Possible Protective Effect of Bone Marrow-Mesenchymal Stem Cells
(BM-MSCs) Against the Remote Liver Injury Induced by Renal Ischemia Reperfusion in Male Albino Rats
Effect of Platelet Rich Plasma (PRP) Injection on the Endocrine
Pancreas of the Experimentally Induced Diabetes in Male Albino Rats: A
Histological and Immunohistochemical Study
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
2. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 2 of 11
Volume 3 • Issue 3 • 1000182
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ISSN:2155-6156 JDM, an open access journal
other dietary sources [11]. Flavonoids are frequently exhibited
antioxidant activity. An increased consumption of antioxidants in the
diet of individuals is strongly recommended [12].
The aim of this work is to evaluate the effect of QCT on the
histological changes which occur in the islet of Langerhans of the STZ-
induced diabetic rats and the possible mechanisms through which
QCT produces its protective effect.
Material and Methods
Animals used
This study was conducted in the Histology department, faculty of
Medicine of El-Minia University. Forty five males albino rats at the age
8-10 weeks, weighting 200-250 grams were used. Animals were housed
in a clean plastic cage and were given food and water ad libitum.
Reagents
1-Streptozotocin (STZ) vial containing 1 g STZ and 220 mg citric
acid was obtained from Sigma Aldrich, which was freshly dissolved in
0.1 mol /1 citrate buffer, pH 6.
2-Querectin (QCT) (3,5,7,3’,4’-pentahydroxyflavone) was obtained
from Sigma Aldrich, dissolved in 0.5 ml of 60% ethanol just before
injection according to manufacturer’s instructions.
Experimental design
Animals were randomly divided into three groups as following:
The control group (group I): It consists of 15 rats which received a
single intra peritoneal injection of citrate buffer saline.
The Diabetic group (group II): It consists of 15 rats in which
diabetes was induced by a single intra peritoneal injection of STZ in a
dose of 75 mg/kg body weight [13].
The QCT-treated group (group III): It consists of 15 rats. Rats
were received a daily intra peritoneal injection of QCT (25 mg/kg body
weight/day). This treatment was started 30 days prior to induction of
diabetes. Induction of diabetes was done by injection of a single dose of
STZ, and then QCT was continued for another 30 days.
In this study, the day of intraperitoneal injection of STZ was
determinated as (day 0) and every other day thereafter. Blood samples
were taken after overnight food deprivation. Samples were taken from
tail veins for monitoring blood glucose levels at 48h and on the day 30
after injection of STZ.
Four rats from the different groups were slowly intravenously
injected with 0.3 ml aqueous buffered solution formed of suspension
of carbon particles (0.5 ml) in normal saline (100 ml), two hours before
the sacrifice. This was to determine the phagocytic uptake of the carbon
particles by the macrophages [14].
At day 30 for all groups rats were sacrificed by decapitation under
light halothane anesthesia, specimen were removed and the splenic
portions (tail) of the pancreas were taken, then dissected and rapidly
fixed in 10% formal saline for 48 hours, then specimens were processed
for morphological and morphometric studies.
For biochemical study
The glucose level was confirmed by the use of One Touch
Glucometer and compatible blood glucose test strips. STZ treated rats
with blood glucose level ≥18 mmol/litre were considered to be diabetic
and used in this study [15].
For light microscopy
The specimens were fixed in 10% neutral-buffered formalin,
dehydrated in a graded ethanol series, cleared in xylene and embedded
in paraffin wax. Some sections (5 μm thick) were stained with
haematoxylin and eosin (H&E). For detection of alpha and beta cells,
other sections were stained with Gomori’s chrome alum hematoxylin-
phloxine stain [16].
For immunohistochemical study
Immunocytochemical staining was performed using
polyclonal rabbit antibodies (anti-cleaved caspase 3 and iNOS).
Immunohistochemistry for active caspase and iNOS was performed
on formalin-fixed, paraffin-embedded tissue. Sections were
deparaffinized, hydrated then washed in 0.1 M phosphate buffer
saline (PBS). Endogenous peroxidases were quenched by treatment
with H2
O2
in methanol (Peroxidase blocking solution) followed by
washing in tris buffer saline (TBS). Non-specific binding of IgG was
blocked using normal goat serum, diluted 1:50 in 0.1% bovine serum
albumin with TBS for 30 minutes. The sections were incubated with
the diluted primary antibodies for cleaved caspase 3 (1:500) and iNOS
(ready to use) overnight at room temperature. Sections then were
washed 3 times each for 5 minutes in buffer and incubated for further
30 minutes with biotinylated goat anti-rabbit secondary antibodies
diluted 1:1000, followed by washing. Following further 30 minutes
incubation with Vectastain ABC kits (Avidin, Biotinylated horse
radish peroxidase Complex) and washing for 10 minutes, the substrate,
diaminobenzidine tetra hydrochloride (DAB) in distilled water was
added for 5-10 min. The enzyme reaction was developed as described
previously. The slides were lightly counterstained by hematoxylin to
gain a good morphological identification of cells, and dehydrated by
passing through ascending concentrations of alcohol then cleared by
xylene. Cover slip using permanent mounting media is put at last. This
substrate gives brown color at the immunoreactive sites [17].
Photography: Olympus light microscopy was used. Slides were
photographed using Olympus digital camera. Images were processed
using Adobe Photoshop.
Morphometric analysis: The procedures utilized a hardware
consisting of a high-resolution color digital camera mounted on an
Olympus BX51 microscope andconnected to a computer. Four sections
were examined from each animal in the different groups.
Quantitative data were collected for 4 parameters
The number of islets per square millimeter of each section:
The islets of the pancreas were counted in H&E slides in random
microscopic areas under 10 high power fields. The number of islets was
assessed by counting all islets per one square millimeter of different
non overlapped fields for the same slide of each animal.
The number of β cells in the islet: The β cells of the pancreas were
counted in chrome alum hematoxylin slides under 40 high power
fields. The number of β cells was assessed by counting all nuclei of the
blue stained cells inside one islet in the field. Approximately 4 islets
were included on each section. In each animal 3 sections were counted
and a total number of 60 islets of each group were counted.
Counting the number of β cells, and the total number of cells in
the pancreatic islets: Chrome alum hematoxylin stained sections were
used to assess the number of β cells and the total number of cells in
the pancreatic islets in 40 high power fields. The number of β cells was
assessed by counting all nuclei of the blue stained cells inside one islet
3. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 3 of 11
Volume 3 • Issue 3 • 1000182
J Diabetes Metab
ISSN:2155-6156 JDM, an open access journal
in the field. The total number of cells in the same islet was calculated by
counting the all nuclei in the islet. Approximately 4 islets were included
on each section. Three sections were used for each animal in the group,
and a total number of 60 islets for each group were counted.
The same islets in the same fields were used for counting both β cells
and the total number of cells. The ratio between number of beta cells
of the islet to the total number of cells in the same islet was calculated
in each experimental group. The Percent of β cells was calculated by
dividing the number of B cells / the total number of cells in each islet
x100.
Data handling and statistics
The mean number (MN) and standard deviation (SD) were
determined for parameter in each group. The significance of differences
observed in these groups was pooled and assessed by the student t-test
Results
Biochemical study
Blood glucose levels of the control group showed normal levels
with a mean of 4.2 ± 0.7 mmol/L throughout the study. In the diabetic
group, there was a significant increase in blood glucose levels 48 h after
STZ injections, and get its highest levels by 30 days after STZ injections
(all p= 0.000). While in the QCT-treated group, there was a significant
decreaseinbloodglucoselevels48hand30daysafterSTZinjections(p=
0.000), compared to the diabetic group. On the other hand, the QCT-
treated group had relatively similar blood glucose levels compared to
controls as there was no significant difference noted either at 48 h or
30 days after STZ injections (p=0.011, p=0.006 respectively) (Table 1).
Histological study
Histological study of pancreas using hematoxylin and eosin: The
control group (group I) showed a normal lobular architecture of the
pancreas. The pancreas had abundant islet of langerhans interspersed
among the pancreatic exocrine acini. The islets appeared lightly stained
than the surrounding acinar cells, with intact Interlobular connective
tissue and interlobular duct (Figure1). Each islet consisted of lightly
stained polygonal cells arranged in cords separated by a network
of blood capillaries. The acinar cells were characterized by its basal
basophilia and apical acidophilia (Figures 2,3).
The pancreatic sections of the diabetic group (group II) showed
marked morphological changes. The border between the endocrine
and exocrine region became indistinct. Inflammatory cells infiltration
through the connective tissue septa and around to the periphery of the
islets (Figure 4). The inflammatory cells were also seen surrounding
ducts, in between the acini and inside the lumen of blood vessels. Most
of these cells were neutrophils, eosinophils and macrophages (Figure
5,6). Blood vessels were seen congested and dilated (Figure 6). Some
islets were completely destroyed leaving empty spaces (Figure 7). The
islet’s cells showed different morphology. Some cells appeared with
nuclear pyknosis and nuclear fragmentation. The degenerated cells
surrounded by empty spaces which filled with amyloid-like material
(Figure 8). The cellular residues were engulfed by the phagocytic cells
leaving empty spaces (Figure 9).
In group III, QCT administration showed improvement in the
previous morphological changes in most of the rats, the border
between exocrine and endocrine portions became distinct (Figure 10).
Many islets showed with an increase in the cellular density along with a
Blood glucose levels (mmol/L)
after 48 hours after 30 days
Mean ± sd p-value Mean ± sd p-value
Control group 4.2± 0.7 4.2±0.5
Diabetic group 18.2± 0.3 0.000c
21.3±0.4 0.000c
QCT- treated group 4.7± 0.1
0.000d
0.011 c 4.6 ± 0.1
0.000d
0.006 c
p < 0.05 is significant, c
versus control group, d
QCT-treated group versus diabetic
group. Values are expressed as means (± SEM) of 10 rat
Table 1: Comparison of blood glucose levels (mmol/L) in the studied groups.
CTPA
1
Figure 1: A Photomicrograph of rat pancreatic tissue of the control group
showing normal lobular architecture. Islets of Langerhans (black arrows) seen
surrounded by the pancreatic acini (PA). Notice the Interlobular connective
tissue (CT) and the interlobular duct (D). (Hx&E x100).
IC
BC
A
Figure 2: A photomicrograph of rat pancreatic tissue of the control group
showing Islet’s cells (IC) forming cords separated by a network of blood
capillaries (BC). Notice the pancreatic acini with its basal basophilia and apical
acidophilia (A). (Hx&E x400).
Figure 3: A photomicrograph of rat pancreatic tissue of the control group
showing the lightly stained polygonal Islet’s cells arranged in cords (blue
arrow). (Hx&E x1000).
4. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 4 of 11
Volume 3 • Issue 3 • 1000182
J Diabetes Metab
ISSN:2155-6156 JDM, an open access journal
reduction in the inflammatory cells infiltration inside the islet (Figures
10,11,12). Some ducts were noticed near islets with some cellular
connection (Figure 13).
Histological study of the pancreas using Gomori’s chrome alum
hematoxylin-phloxine: The pancreatic islets of the control group
showed that most of the cells were β-cells which stained deep blue filled
the interior of the islet, while α-cells appeared pink to red and arranged
in clusters scattered either between β -cells or at the periphery of the
islets (Figure14).
The Diabetic group (group II), the islets showed degenerative
changes, especially at the center with decrease in the density of
bluish stained β cells. The remaining cells showed nuclear shrinkage
and pyknosis. Pink to red stained alpha cells were still present at the
periphery of islet and in between β cells (Figure 15).
Group III showed improvement of islet morphology which
approached the corresponding healthy pancreatic sections. There was
also a relative increase in the β-cell mass (Figure 16).
Histological study of pancreatic macrophages using charcoal:
Macrophages were monitored by charcoal injection (phagocytes
Figure 4: A photomicrograph of rat pancreatic tissue of the diabetic group
showing the indistinct boundary between the endocrine and exocrine part (blue
arrow). Notice inflammatory cells (red arrows) infiltrating through connective
tissue septae (CT), islet area (IS) and around the duct (D). (Hx&E x100).
Figure 5: A photomicrograph of rat pancreatic tissue of the diabetic group
showing inflammatory cells (blue circle) surrounding duct (D) and between
acini (A). (Hx&E X400).
Figure 6: A photomicrograph of rat pancreatic tissue of the diabetic group
showing some congested and dilated blood vessels (BV) with inflammatory
cells infiltration (inset). (Hx&E X100).
Figure 7: A photomicrograph of rat pancreatic tissue of the diabetic group
showing completely destroyed islets leaving empty spaces (black arrows).
(Hx&E X100).
8
Figure 8: A photomicrograph of rat pancreatic tissue of the diabetic group
showing degenerated islet’s cells with nuclear pyknosis and nuclear
fragmentation (Inset). Notice the empty spaces leaved after cell degeneration
filled with amyloid-like material (A). (Hx&E x1000).
9
Figure 9: A photomicrograph of rat pancreatic tissue of the diabetic group
showing the inflammatory cells infiltration inside the islet (long arrows). Noticed
cellular residues within the cytoplasm of phagocytic cells (short arrows). The
phagocytic cells are surrounded by empty spaces. (HX&E X1000).
5. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 5 of 11
Volume 3 • Issue 3 • 1000182
J Diabetes Metab
ISSN:2155-6156 JDM, an open access journal
The QCT-treated group (group III), the labeled cells were markedly
decreased all over the pancreatic sections, especially in the islet region
compared to the previous group (Figure19).
Immunohistochemical study
Immunohistochemical study of the rat pancreatic tissues
using iNOS: Sections of the control group displayed negative iNOS
immunoreactivity in the islet cells, the acini and in the endothelium of
the blood vessels (Figure 20).
consider carbon particles of charcoal as a foreign body and uptake
them so their cytoplasm displayed yellowish - brown granules).
In the control group (group I), the islet having charcoal injected
blood vessels in between the islet’s cells and in between acini with no
labeled macrophage seen in the islet (Figure 17).
The Diabetic group (group II), the macrophages in the sections of
this group appeared widely distributed when compared to the control
group. They were more frequently increased in the islet’s region.
The labeled cells were large with irregular outline. Their cytoplasm
displayed yellowish brown charcoal granules (Figure 18).
10
Figure 10: A Photomicrograph of rat pancreatic tissue of the quercetin treated
group showing many islets with distinct border from surrounding exocrine
part (black arrows). Notice presence of ducts near islets (red arrows). (Hx&E
x100).
11
Figure 11: A Photomicrograph of rat pancreatic tissue of the quercetin treated
group showing increase islet cell density. Notice reduction in the inflammatory
cells infilteration (blue arrow indicates an eosinophil). (Hx&E x400).
Figure 12: A Photomicrograph of rat pancreatic tissue of the quercetin treated
group showing islet cells resemble normal. (Hx&E X1000).
IS
D
13
Figure 13: A photomicrograph of rat pancreatic tissue of the quercetin treated
group showing connection between the duct (D) and islet cells (IS) (blue
arrow). (Hx&E x400).
14
Figure 14: A Photomicrograph of rat pancreatic tissue of the control group
showing (β) cells stained deep blue filling the interior of the islet(blue arrows)
,while α-cells stained pink to red scattered mainly at the periphery of the islets
and between (β) cells(red arrows). (chrome alum Hx.X 400).
Figure 15: A Photomicrograph of rat pancreatic tissue of the diabetic group
showing decreased cellular density, the degenerated cells are showed with
nuclear shrinkage and pyknosis (black arrows) mostly in the center of the islet.
Notice pink stained alpha cells at the periphery of islet (red arrows). (chrome
alum Hx. X400).
6. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 6 of 11
Volume 3 • Issue 3 • 1000182
J Diabetes Metab
ISSN:2155-6156 JDM, an open access journal
In the diabetic group (group II), STZ administration caused
changes in the expression of iNOS in the pancreatic tissue. Sections
of this group displayed positive immunoreactivity in the cytoplasm of
some degenerated islet cells and the inflammatory cells infiltrating the
islets. Some endothelial cells of the blood vessels and some acinar cells
also showed positive immunoreactivity (Figure 21).
IntheQCTtreatedgroup(groupIII),therewasnoimmunoreactivity
for iNOS in islet and acini but faint expression was still noticed in the
endothelium of the blood vessels (Figure22).
Immunohistochemical study of the rat pancreatic tissues using
activated (cleaved) Caspase 3: No detectable immunolabeling for
activated caspase 3 in the pancreatic sections of the control group
(Figure 23).
In the diabetic group (group II), STZ administration caused
changes in the expression of active caspase 3 in the rat pancreas. There
was obvious high immunoreactivity for activated caspase 3 in the islets.
The expression in the islet showed a pattern of heterogeneity; most of
the islet’s cells had shown both cytoplasmic and nuclear expression
while others showed only cytoplasmic expression. Few macrophage
like cells showed positive immunoreactivity (Figure 24).
Figure 16: A Photomicrograph of rat pancreatic tissue of the quercetin treated
group showing relatively numerous β-cells (blue arrows), notice α cells at the
periphery of islet(red arrows). (chrome alum Hx. X400).
18
Figure 17: A Photomicrograph of rat pancreatic tissue of the control group
showing an islet having charcoal injected blood vessels in between islet’s cells
(lower inset)and between acini (upper inset) (arrows). (X400).
Figure 18: A Photomicrograph of rat pancreatic tissue of the diabetic group
showing an islet having charcoal labeled macrophages. “The labeled cells”
are large with irregular outline and their cytoplasm displayed yellowish brown
charchol granules (arrows). (X 1000).
Figure 19: A Photomicrograph of rat pancreatic tissue of the quercetin
treated group showing an islet having reduced number of charcoal labeled
macrophage (arrow). (X1000).
Figure 20: A Photomicrograph of rat pancreatic tissue of the control group
immunostained for iNOS showing negative immunoreactivity in the islet cell,
the acini and endothelium of blood vessels (inset). (immunohistochemistry
counter stain Hx x1000).
12
Figure 21: A Photomicrograph of rat pancreatic tissue of the diabetic
group immunostained for iNOS showing positive immunoreactivity in the
inflammatory cells (blue arrows), and macrophage like cells (red arrows)
infiltrating the islet. Positive immunoreactivity seen aslo in the degenerated
islet cells (white arrow). Notice positive immunoreactivity in the endothelium
of blood vessel (upper inset) and in some acinar cells (lower inset). (x1000).
7. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 7 of 11
Volume 3 • Issue 3 • 1000182
J Diabetes Metab
ISSN:2155-6156 JDM, an open access journal
IntheQCT-treatedgroup(groupIII),theprofileofactivatedcaspase
3 expression in the pancreas was changed after QCT administration
when compared to the previous group. There was marked decline in
the activated caspase 3 immunolabeling in the islet region (Figure 25).
The morphometric results
Morphometric analysis of the number of islets per square
millimeter: There was a significant decrease in the number of
pancreatic islets/mm2
of the STZ induced diabetic group compared to
the control group (p=0.000). On the other hand, there was a significant
increase in the number of the islets of QCT-treated group compared
to the STZ induced diabetic group (p=0.000). There was no significant
difference in the number of the islets in QCT-treated group compared
to control group (p=0.258) (Table 2).
Morphometric analysis of the number of β cells per islet: There
was a significant decrease in the number of B cells in the islet of the
STZ induced diabetic group compared to the control group (p=0.000).
On the other hand, there was a significant increase in the number of
β Cells of QCT-treated group compared to the STZ induced diabetic
group (P=0.000). Meanwhile, there was no significant difference of a
number of β cells in QCT-treated group compared to the control group
(p=0.366) (Table 3).
Morphometric analysis of the total number of cells in each islet:
There was a significant decrease in the total number of cells in each
islet of the STZ induced diabetic group compared to the control group
(p=0.000). On the other hand, a significant increase in the total number
of cells in each islet of the QCT-treated group compared to the STZ
induced diabetic group (p=0.002). There was no significant difference
of the total number of cells in QCT-treated group compared to control
group (p=0. 447) (Table 4).
Percent of B cells to the total number of cells in each islet: The
percent of β cells in the control group ranged from 60%-75%.There was
a decrease in percent of β cells (28%-50%) after STZ induced diabetes,
while in QCT-treated group an increase in the percent of β Cells in
each islet (50%-60%) was observed compared to the STZ induced
diabetic group.
Discussion
In this study a high dose of STZ was used to induce DM1. High
dose treatment of STZ induced a more rapid loss of insulin secretion
and therefore more rapid onset of diabetes compared to low dose
treatment [18]. A dose of 60-75 mg/kg of STZ causes destruction of islet
cells [19]. Destruction of β-cell in rat’s pancreas starts 3 days after STZ
administration and reaches its peak at 3-4 weeks [20]. In this study, the
blood glucose level of diabetic group had started to increase at 48h after
injection of STZ (18.2 ± 0.3mmol/l) and reached the highest level at 30
day after injection (21.3 ± 0.4 mmol/l) this was in comparison to the
control group (4.1 ± 0.4 mmol/l). QCT treatment prior to induction
of diabetes was found to have beneficial effect on hyperglycemia,
blood glucose level returned to a relatively normal value. This result
in agreement with Rivera et al. [21], who found that quercetin has a
beneficial effects on blood glucose level in Obese rats which received a
daily dose of 2 or 10 mg/kg of quercetin, orally for 10 weeks.
Figure 22: A Photomicrograph of rat pancreatic tissue of the quercetin treated
group immunostained for iNOS showing negative immunoreactivity in the
islet and the acini. Inset showing faint expression in the endothelium of blood
vessel (arrow). (x1000).
IC
Figure 23: A photomicrograph of pancreatic tissue of the control group for
caspase 3 showing negative immuostained immunoreactivity in the islet’s
cells. (x1000).
Figure 24: A photomicrograph of pancreatic tissue of the diabetic group
immuostained for caspase 3 showing positive immunoreactivity in cytoplasm
of some islet cells (red circles).Notice nuclear expression of the other cells
(blue circles). Notice positive stained macrophage like cell (inset). (x1000).
Figure 25: A photomicrograph of pancreatic tissue of the quercetin treated
group immuostained for caspase 3 showing faint immunoreactivity in the islet
cells (IC). (X1000).
8. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 8 of 11
Volume 3 • Issue 3 • 1000182
J Diabetes Metab
ISSN:2155-6156 JDM, an open access journal
In this study the histological observations using H&E stain
showed that the pancreatic islets from control group displayed normal
histological features. In the diabetic group, marked morphological
changes were observed including breakdown of microanatomical
features, marked inflammatory cells infiltration. The islets showed
marked degeneration of their cells. These degenerated cells appeared
with nuclear pyknosis, fragmentation, and others showed cytoplasmic
vacuolation. Cellular residues were seen within the cytoplasm of
phagocytic cells. Phagocytic cells cleaning resulted in empty spaces.
In some sections the empty spaces leaved after cell degeneration was
seen to be filled with amyloid like material. In few animals, the islets
were completely destroyed leaving empty spaces which were previously
occupied by islet cells. The present study reinforced the previous
recorded result which mentioned that diabetes caused extensive β-cell
degranulation and decreased cellular density in pancreatic islets [2].
Selective destruction of insulin producing β cells could be explained by
Blairetal.[22],whoreportedthatDM1ischaracterizedbyinflammatory
reaction in and around the islets followed by β cell degeneration.
Inflammatory reaction is caused by inflammatory cells, these cells
being the humoral mediators of immunologic process and release of
various cytokines. Cytokines are immunological effector molecules
responsible for inhibition of insulin secretion from pancreatic β cells
and inducing β cell destruction [23]. Amyloid; an insoluble fibrous
protein, studies have shown that the amyloid deposition is associated
with mitochondrial dysfunction and lead to the generation of reactive
oxygen species (ROS) which can initiate a signaling pathway leading to
apoptosis [24].
In the present work, histological finding of the pancreas of QCT-
treated group showed that QCT administration improved the previous
degenerative changes in most of the rats. Many islets were showed
with increased cells along with a reduction in the inflammatory
cells infiltration. This was in agreement with Adewole et al. [2], who
found that in diabetic rats treated with QCT, there were no evidence
of inflammatory cells infiltration and the islets were observed with
increase in granulation intensity.
There was an interesting finding in this work which was the
presence of cellular connections between some ducts and the islets
cells, this might be explained by Xiu et al. [25], who reported that islet
stem cells or progenitor cells exist in the adult pancreas are located
in or near the pancreatic duct. Some stimuli can trigger these stem
cells to differentiate into endocrine cells. The reverse of diabetes in
diabetic animals was due to formation of new islets from ductal cells
[26]. From these facts it could be suggested that QCT may trigger duct
stem cell to differentiate into endocrine cells which were confirmed by
morphological and morphometric results in this study. This study may
add a new mechanism of the protective role of QCT against diabetes. So
the newly generated islets may have formed from the ductal precursor
cells.
Histological finding of the pancreatic tissue using chrome alum
heamatoxylin of the control group showed bluish stained β cells filling
the interior of the islet, while pink stained α-cells are arranged in
clusters scattered mainly at the periphery of the islets and also between
β cells. Morphological and morphometrical study of the diabetic group,
degenerative changes were seen especially at the center of islets with
decrease number of the bluish stained β cells while the pink stained
alpha cells still present at the periphery of the islet, the injection of STZ
caused a significant decrease in the number of pancreatic islets/mm2
and the number of β cells in the islet as compared to control group.
This was in agreement with Al-Khalifa et al. [27], who reported that
a significant decrease in the number of β cells in all diabetic groups as
compared with the respective control groups. In QCT-treated group,
morphmetric results showed that there was a significant increase in the
number of the islets/mm2
and the number of β cells in islet compared
to diabetic group. There was no significant difference in the number
of islets/mm2
compared to the control group. There was a significant
decrease in percent of β cells (28%-50%) in diabetic group, while in
QCT-treated group a significant increase in percent of β Cells in each
islet (50%-60%) compared to the diabetic groups. The QCT may act
on islet functions, increasing the number of pancreatic islets and
stimulating insulin release in diabetic rats [28].
For further assessment of the protective role of QCT on diabetes
and its mechanisms for the protection, histological study of the
pancreatic macrophages using charcoal and immunohistochemical
study of rat pancreatic tissues using iNOS and caspase 3 were done.
Intravenous injection of charcoal has been shown to provide a
method for visualizing the phagocytes. In this work, macrophages
in sections of diabetic group appeared more frequently and widely
distributed when compared to the control group. The labeled cells were
large with irregular outline. Their cytoplasm displayed yellowish brown
charchol granules. Macrophages were present in many pancreatic
islets during insulitis. In approval with speculations of the role of
macrophages in the pathogenesis of DM1, macrophages are present in
islets and in experimental conditions macrophages are able to engulf
insulin granules from damaged β cells [29]. Islet cytokines and other
inflammatory mediators elicit activation of vascular endothelium [30].
Endothelial activation in the pancreas leads to increased adhesion,
extravasations of circulating leukocytes and presentation of target
antigens by infiltrated macrophages and perhaps by endothelial cells
themselves. The activated T-cells first invade the islets leading to
insulitis. This is followed by destruction of the islets, mediated by a
complex interaction between the activated lymphocytes, cytokines, and
macrophages. Cytokines produced by islet infiltrating macrophages
may contribute to β cell damage by inducing the production of oxygen
free radicals in the islets. These cytokines, which are released from
MN ± SD p-value
Control group 4.1 ± 0.23
Diabetic group 1 ±0.85 0.000c
QCT-treated group 3.3 ± 0.28
0.258c
0.000d
p < 0.05 is significant, c
versus control group, d
QCT-treated group versus diabetic
group
Table 2: The number of islets/mm² in the control and experimental groups.
p < 0.05 is significant, c versus control group, d
QCT-treated group versus diabetic
group
Table 3: The number of β cells per islet in the control and experimental groups.
MN ± SD p-value
Control group 86.7 ± 34.09
Diabetic group 19.66 ±6.59 0.000c
QCT-treated group 78.46 ± 25.21
0.366c
0.000d
p < 0.05 is significant, c versus control group, d
QCT-treated group versus diabetic
group
Table 4: The total number of all cells of islet in the control and experimental groups.
MN ± SD p-value
Control group 17.06 ± 43.96
Diabetic group 60.53 ± 22.55 0.000c
QCT-treated group 06.20 ±44.95
0.447c
0.002d
9. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 9 of 11
Volume 3 • Issue 3 • 1000182
J Diabetes Metab
ISSN:2155-6156 JDM, an open access journal
activated macrophages, are believed to be toxic to β cells [31]. The toxic
effect produced by activated macrophages on β cells is thought to be
mediated by the superoxide anion and hydrogen peroxide and β cell
is very sensitive to the production of free radicals because islet cells
exhibit very low free radical scavenging activity [32]. In QCT-treated
group in this study, the charcoal labeled macrohages were markedly
decreased all over the pancreatic sections, especially in the islet region
compared to the diabetic group suggested that QCT had a protective
role as anti-inflammatory in decreasing the mediators of inflammation
in diabetes. This finding was in the same line of Overman et al. [33],
who reported that QCT reduced the inflammation in human and
prevent the mediator of this inflammation.
It is also believed that possible mediator of pancreatic β cell
damage is radical NO and iNOS is the most involved of NOS isoforms
in immune mediated β cell damage. High level of NO produced by
iNOS is related to pancreatic β cell dysfunction and apoptosis [34].
A significant increase of NO synthesized by iNOS participates in
provoking inflammatory process and acts synergistically with other
inflammatory mediators and compounds able to reduce NO production
by iNOS may be attractive as anti-inflammatory agents [35]. In this
study iNOS might play a role in the protective effect noticed after QCT
treatment in diabetes, so this study analyzed iNOS expression in the
pancreatic tissue under diabetic conditions as well as it was examined
upon treatment with QCT. Immunocytochemical study using iNOS
showed that in the control group negative iNOS immunoreactivity was
noticed in either the islets cells, acinar cells or the blood vessels. This in
agreement with Liu et al. [36], who reported that NO produced under
physiological conditions contributes to cellular functions in pancreatic
beta-cells just like in other cells, but it is not determined which type
nitric oxide synthase isoform produces NO under physiological
conditions, presence of iNOS in pancreas and islets under physiological
conditions has not been exactly elucidated. In this study, the diabetic
group showed positive iNOS immunoreactivity in the inflammatory
cells infiltrating the islets, the endothelium of blood vessels and in some
acinar cells. There was an intense immunostaining for iNOS in STZ
induced diabetic rat as compared with the control rats. This enhanced
iNOS levels induced by STZ suggests the oxidative stress which may led
to the degeneration of β cells of the pancreas. The previous results were
in agreement with Johannesen et al. [37], who reported that there is a
high level of iNOS expression in the diabetic animals but he suggested
that NO is necessary but not sufficient by itself in cytokine mediated
selective β cell destruction. NO production in β cells, macrophages,
ductal cells, and endothelial cells has been considered [38]. Ductal cells
are potential source of NO production in human islets which have
been infiltrated by cytokine releasing immunocytes [39]. The present
data indicate that the possible contribution of β cell iNOS is restricted
to the close vicinity of macrophages. The other possible site of iNOS
expression is the endothelium. In fact several studies have shown that
endothelial cells respond to cytokine challenge with sustained NO
release [40]. This indicates that macrophages themselves express iN0S.
In addition, macrophages may have induced adjacent endothelial or
endocrine islet cells by inflammatory mediators to secrete NO, Such
mediators are IL-l and TNF [41]. The expression of iNOS in islet
β cells is mediated by the cytokines interleukin-1β (IL-1β), tumor
necrosis factor-α (TNF-α), and interferon-γ (IFNγ), produced by
lymphocytes and macrophages that are known to infiltrate the islets
during the development of DM1. It was reported that endogenous
NO is involved in formation of pancreatic edema by increasing the
vascular permeability and protein extravasation. NO, participate in
the development of pancreatic microcirculatory failure [23,42]. This
study showed that in the QCT-treated group there was negative iNOS
immunoreactivity in the islet and acini with faint expression noticed
in the endothelium of some blood vessels. This finding suggesting the
ability of QCT to function as an antioxidant against nitrosative stress.
This was in the same line with the study of Kleemann et al. [43], who
has been shown that the pharmacological inhibition of iNOS protects
against β cell damage and reduces the sensitivity of animals against
induction of diabetes. Polyphenols inhibit NO release by suppressing
NOS enzymes expression and/or NOS activity [44]. Flavonoids
appeared to be a potential therapeutic agent against DM1, and QCT
has been shown to exert protective effect on β cells by different
mechanisms including blocking iNOS gene expression. Caspases play
a key role in apoptosis [45]. Immunohistochemical localization of
activated (cleaved) caspase 3 in rat pancreatic tissues as an indicator of
apoptosis was performed. In this study no detectable immunolabeling
for activated caspase 3 in the pancreatic sections of the control group
but in diabetic group there was high expression of active caspase 3.
There was obvious high immunoreactivity for activated caspase 3 in
the islets. The expression in the islet showed a pattern of heterogeneity
i.e. most of the islet cells had shown both cytoplasmic and nuclear
expression while others showed only cytoplasmic immunoreactivity.
Few macrophage like cells showed positive immunoreactivity. STZ
induced pancreatic β-cell death is associated with oxidative stress
caused by the production of excess intracellular ROS furthermore, STZ
may damage pancreatic tissue via imposition of oxidative as well as
nitrosative stresses, which in turn can induce apoptosis in pancreatic
cells with an invasion of the islets by macrophages and T cells termed
insulitis. These activated inflammatory cells produce cytokines, such as
IL-1β, IFNγ, and TNF-α, which cause progressive destruction of most
β-cells via apoptosis, leading to an absolute deficiency of insulin [46].
Based on animal studies, it is assumed that decreased beta cell mass
in DM1 is due to increased beta cell apoptosis [47]. Beta cells are also
vulnerable to apoptosis when exposed to glucose concentrations of
approximately 11 mmol/l (200 mg/dl) or higher through mechanisms
that include β cell expression and the action of IL-1 [48]. In contrast to
this study, Reddy et al. [49], reported that caspase-3 immunoreactivity
predominantly intra islet macrophages but not islet cells, suggesting
that apoptotic β cells are cleared rapidly after onset of diabetes. The
discrepancy between the present results and theirs might be due to
the different stages of insulinitis to which islets cells responded. In the
QCT treated group, there was marked decline in the activated caspase 3
immunolabeling in the islet region. This can be explained by Ardestani
and Yazdanparast [50], who reported that the activation of NF-κB by
acute oxidative stress may be the critical signal initiating the cascade
of events leading to β-cell death and DM1. Thus, understanding these
ROS-induced signal pathways in the immune and inflammatory
response becomes essential in finding preventive treatments. Therapy
that can target the activation of NF-κB may be an effective therapeutic
tool in finding treatments to cure DM1. In view of their anti-
inflammatory and antioxidant abilities and their capacity to modulate
NF-κB signaling pathways which lead to apoptosis, it is hypothesized
that flavonoids as QCT hold great promise as potential therapeutic
agents for controlling the onset of DM1.
In conclusion, the morphological and morphometrical findings
suggested that the administration of QCT to diabetic rats causes
beneficial effect in terms of regeneration of β cells in damaged pancreas.
Hence it is concluded that QCT possess preventive and curative effect
on STZ induced diabetes in rats, so it can be used as a herbal medicine
to protect the pancreatic β cells. This protective effect may be through
its inhibitory effect on iNOS levels and apoptosis. QCT may have a
10. Citation: Rifaai RA, El-Tahawy NF, Saber EA, Ahmed R (2012) Effect of Quercetin on the Endocrine Pancreas of the Experimentally Induced Diabe-
tes in Male Albino Rats: A Histological and Immunohistochemical Study. J Diabetes Metab 3:182. doi:10.4172/2155-6156.1000182
Page 10 of 11
Volume 3 • Issue 3 • 1000182
J Diabetes Metab
ISSN:2155-6156 JDM, an open access journal
stimulatory effect on ductal stem cells to differentiate and regenerate
islet cells.
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