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.
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.
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.
Diabetes is a multifactorial disease leading to several complications, and therefore demands a multiple therapeutic approach. Patients of diabetes either do not make enough insulin or their cells do not respond to insulin. In case of total lack of insulin, patients are given insulin injections. Whereas in case of those where cells do not respond to insulin many different drugs are developed taking into consideration possible disturbances in carbohydrate-metabolism. For example, to manage post-prandial hyper-glycaemia at digestive level, glucosidase inhibitors such as acarbose, miglitol and voglibose are used. These inhibit degradation of carbohydrates there by reducing the glucose absorption by the cells. To enhance glucose uptake by peripheral cells biguanide such as metformin is used. Sulphonylureas, like glibenclamide, is insulinotropic and work as secretogogue for pancreatic cells. Although several therapies are in use for treatment, there are certain limitations due to high cost and side effects such as development of hypoglycemia, weight gain, gastrointestinal disturbances, liver toxicity etc. Based on recent advances and involvement of oxidative stress in complicating diabetes mellitus, efforts are on to find suitable antidiabetic and antioxidant therapy.
Medicinal plants are being looked upon once again for the treatment of diabetes. Many conventional drugs have been derived from prototypic molecules in medicinal plants. Metformin exemplifies an efficacious oral glucose-lowering agent. To date, over 400 traditional plant treatments for diabetes have been reported, although only a small number of these have received scientific and medical evaluation to assess their efficacy. The hypoglycemic effect of some herbal extracts has been confirmed in human and animal models of type 2 diabetes. The World Health Organization Expert Committee on diabetes has recommended that traditional medicinal herbs be further investigated. The present paper Reviews the Role of Insulike tablets developed by R&D cell of Lactonova Nutripharm Pvt Ltd. Hyderabad in the role of herbal nutraceutical drug INSULIKE, A nutriphenotypic approach for the treatment of diabetes.
D-002 treatment attenuates esophagitis in a model of chronic gastro-esophagea...iosrphr_editor
To investigate the effects of D-002 (beeswax alcohols) on esophagitis induced by chronic gastroesophageal reflux (c-GER) in rats. Rats were randomized into a sham and five groups subjected to c-GER: a positive vehicle control, three D-002 (50, 100 and 200 mg/kg), and one omeprazole (20 mg/kg) group, all treated orally for seven days. cGER was induced by ligation of the junction between the forestomach and the duodenal side of the pylorus. Esophageal lesions index (ELI), esophageal malondialdehyde (MDA) and sulfhydril groups (SHG) concentrations were assessed. The positive control group exhibited macroscopically signs of esophageal injury assessed in term of ELI, which was significantly higher than in the negative control. D-002 (50, 100 and 200 mg/kg) reduced the ELI, showing 30.5, 72.9 and 76.4% protection, respectively; and also significantly attenuated the increased MDA (37.4, 63.6 and 94.2%, respectively) and SHG (16.6, 41.6 and 72.9%, respectively) esophageal concentrations versus the positive control. Omeprazole decreased the ELI (80.2%), MDA (99.3%) and SH (85.4%) esophageal concentrations. As conclusions, this study suggest that repeated oral administration with D-002 protects against reflux esophagitis and decreases esophageal lipid peroxidation and protein oxidation markers in rats with c-GER.
Curcumin, the compound responsible for the yellow color of turmeric has much more to offer than just its color. Curcumin comes with a plethora of health benefits which makes it a hot topic in the nutraceutical industry. Unleash the world of curcumin and see the reasons why you need to spice it up!
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
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.
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.
Diabetes is a multifactorial disease leading to several complications, and therefore demands a multiple therapeutic approach. Patients of diabetes either do not make enough insulin or their cells do not respond to insulin. In case of total lack of insulin, patients are given insulin injections. Whereas in case of those where cells do not respond to insulin many different drugs are developed taking into consideration possible disturbances in carbohydrate-metabolism. For example, to manage post-prandial hyper-glycaemia at digestive level, glucosidase inhibitors such as acarbose, miglitol and voglibose are used. These inhibit degradation of carbohydrates there by reducing the glucose absorption by the cells. To enhance glucose uptake by peripheral cells biguanide such as metformin is used. Sulphonylureas, like glibenclamide, is insulinotropic and work as secretogogue for pancreatic cells. Although several therapies are in use for treatment, there are certain limitations due to high cost and side effects such as development of hypoglycemia, weight gain, gastrointestinal disturbances, liver toxicity etc. Based on recent advances and involvement of oxidative stress in complicating diabetes mellitus, efforts are on to find suitable antidiabetic and antioxidant therapy.
Medicinal plants are being looked upon once again for the treatment of diabetes. Many conventional drugs have been derived from prototypic molecules in medicinal plants. Metformin exemplifies an efficacious oral glucose-lowering agent. To date, over 400 traditional plant treatments for diabetes have been reported, although only a small number of these have received scientific and medical evaluation to assess their efficacy. The hypoglycemic effect of some herbal extracts has been confirmed in human and animal models of type 2 diabetes. The World Health Organization Expert Committee on diabetes has recommended that traditional medicinal herbs be further investigated. The present paper Reviews the Role of Insulike tablets developed by R&D cell of Lactonova Nutripharm Pvt Ltd. Hyderabad in the role of herbal nutraceutical drug INSULIKE, A nutriphenotypic approach for the treatment of diabetes.
D-002 treatment attenuates esophagitis in a model of chronic gastro-esophagea...iosrphr_editor
To investigate the effects of D-002 (beeswax alcohols) on esophagitis induced by chronic gastroesophageal reflux (c-GER) in rats. Rats were randomized into a sham and five groups subjected to c-GER: a positive vehicle control, three D-002 (50, 100 and 200 mg/kg), and one omeprazole (20 mg/kg) group, all treated orally for seven days. cGER was induced by ligation of the junction between the forestomach and the duodenal side of the pylorus. Esophageal lesions index (ELI), esophageal malondialdehyde (MDA) and sulfhydril groups (SHG) concentrations were assessed. The positive control group exhibited macroscopically signs of esophageal injury assessed in term of ELI, which was significantly higher than in the negative control. D-002 (50, 100 and 200 mg/kg) reduced the ELI, showing 30.5, 72.9 and 76.4% protection, respectively; and also significantly attenuated the increased MDA (37.4, 63.6 and 94.2%, respectively) and SHG (16.6, 41.6 and 72.9%, respectively) esophageal concentrations versus the positive control. Omeprazole decreased the ELI (80.2%), MDA (99.3%) and SH (85.4%) esophageal concentrations. As conclusions, this study suggest that repeated oral administration with D-002 protects against reflux esophagitis and decreases esophageal lipid peroxidation and protein oxidation markers in rats with c-GER.
Curcumin, the compound responsible for the yellow color of turmeric has much more to offer than just its color. Curcumin comes with a plethora of health benefits which makes it a hot topic in the nutraceutical industry. Unleash the world of curcumin and see the reasons why you need to spice it up!
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
Igennus are excited to announce the launch of our new product, Longvida® Curcumin. During this webinar, Dr Bailey reviews the research behind the therapeutic use of curcumin and why Longvida is the world’s most advanced formulation of the nutrient.
Curcumin is a polyphenol compound obtained from the rhizome of Curcuma longa, also known as turmeric. This Indian spice has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Curcumin is well documented for its antioxidant, anti-inflammatory and anti-cancer activities. Although it has been shown to be safe at high doses (12g/d), it is poorly absorbed, undergoes rapid intestinal and hepatic metabolism and is rapidly eliminated from the body. As such, standard curcumin demonstrates poor bioavailability, even at high doses, limiting its therapeutic potential.
After much research and discussion (it’s a big and complicated topic!) between the Igennus nutrition scientists, the decision as to which type of curcumin we would use for our Synergistic Nutrients range was actually a very straightforward one. Longvida Curcumin utilises a novel delivery system (SLCP), which protects curcumin from the harsh environment of the stomach and promotes its rapid absorption into the bloodstream and target tissues, even at low doses – resulting in an incredible 285x superior bioavaibility compared with standard curcumin, 65x higher peak plasma levels and 7x longer-lasting action. Longvida is the only formulation proven to deliver high levels of free form, unconjugated curcumin, into the bloodstream. Free form curcumin is the form required for therapeutic benefits, and the only form proven to cross the blood brain barrier.
This webinar covers:
- What curcumin is, what it does and how?
- Why free form curcumin is essential for therapeutic effects
- The research and current evidence for Longvida Curcumin’s unique health benefits
- How Longvida overcomes significant bioavailability issues associated with curcumin use
- To who, why and when you should recommend curcumin
…and more.
Effect of emulin on blood glucose in type 2 diabetics - https://emulincanada.comAj Martirano
Effect of Emulin on Blood Glucose in Type 2 Diabetics https://emulincanada.com
,effect of emulin on blood glucose in type 2 diabet ,emulin diabetes ,igalen emulin diabetes ,emulin type 2 diabetes
Contains curcuminoids such as curcumin (diferuloylmethane), demethoxycurcumin, and bisdemethoxycurcumin Free radical mediated Useful against skin infections; Treat boils efficiently
Protects skin from the damaging effects of UV B radiation
Reduce formation of wrinkles on the skin; anti-ageing
Curcumin for Cancer Prevention & Cure 09370322999Shibu Thankachan
Call 09370322999 to knore more on our product Curcumin C3 Power™ which is the best solution for Cancer prevention
Cancer is a term used for a broad group of diseases involving unregulated cell growth. There are more than hundred types of cancerous growth of cells that can affect almost any part of the body including brain, lung, breast, skin, blood, colon or cervix.
Up to 40% of all cancer deaths can be prevented by eliminating tobacco use, improving diets and physical activity, lowering alcohol consumption, eliminating workplace carcinogens and immunizing against Hepatitis B virus and human papillomavirus. Also a large proportion of cancer can be cured if detected early.
Lot of Researches have shown that Curcumin the active ingredient in turmeric has emerged as a potent multimodal cancer-preventing agent. Daily intake of required amount of Curcumin can go a long way in preventing cancer
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.
CR-Submanifolds of a Nearly Hyperbolic Cosymplectic Manifold with Semi-Symmet...iosrjce
We consider a nearly hyperbolic cosymplectic manifold and we study some properties of CRsubmanifolds
of a nearly cosymplectic manifold with a semi-symmetric semi-metric connection. We also obtain
some results on 휉−horizontal and 휉 −vertical CR- submanifolds of a nearly cosymplectic manifold with a semisymmetric
semi-metric connection and study parallel distributions on nearly hyperbolic cosymplectic manifold
with a semi-symmetric semi-metric connection.
Igennus are excited to announce the launch of our new product, Longvida® Curcumin. During this webinar, Dr Bailey reviews the research behind the therapeutic use of curcumin and why Longvida is the world’s most advanced formulation of the nutrient.
Curcumin is a polyphenol compound obtained from the rhizome of Curcuma longa, also known as turmeric. This Indian spice has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Curcumin is well documented for its antioxidant, anti-inflammatory and anti-cancer activities. Although it has been shown to be safe at high doses (12g/d), it is poorly absorbed, undergoes rapid intestinal and hepatic metabolism and is rapidly eliminated from the body. As such, standard curcumin demonstrates poor bioavailability, even at high doses, limiting its therapeutic potential.
After much research and discussion (it’s a big and complicated topic!) between the Igennus nutrition scientists, the decision as to which type of curcumin we would use for our Synergistic Nutrients range was actually a very straightforward one. Longvida Curcumin utilises a novel delivery system (SLCP), which protects curcumin from the harsh environment of the stomach and promotes its rapid absorption into the bloodstream and target tissues, even at low doses – resulting in an incredible 285x superior bioavaibility compared with standard curcumin, 65x higher peak plasma levels and 7x longer-lasting action. Longvida is the only formulation proven to deliver high levels of free form, unconjugated curcumin, into the bloodstream. Free form curcumin is the form required for therapeutic benefits, and the only form proven to cross the blood brain barrier.
This webinar covers:
- What curcumin is, what it does and how?
- Why free form curcumin is essential for therapeutic effects
- The research and current evidence for Longvida Curcumin’s unique health benefits
- How Longvida overcomes significant bioavailability issues associated with curcumin use
- To who, why and when you should recommend curcumin
…and more.
Effect of emulin on blood glucose in type 2 diabetics - https://emulincanada.comAj Martirano
Effect of Emulin on Blood Glucose in Type 2 Diabetics https://emulincanada.com
,effect of emulin on blood glucose in type 2 diabet ,emulin diabetes ,igalen emulin diabetes ,emulin type 2 diabetes
Contains curcuminoids such as curcumin (diferuloylmethane), demethoxycurcumin, and bisdemethoxycurcumin Free radical mediated Useful against skin infections; Treat boils efficiently
Protects skin from the damaging effects of UV B radiation
Reduce formation of wrinkles on the skin; anti-ageing
Curcumin for Cancer Prevention & Cure 09370322999Shibu Thankachan
Call 09370322999 to knore more on our product Curcumin C3 Power™ which is the best solution for Cancer prevention
Cancer is a term used for a broad group of diseases involving unregulated cell growth. There are more than hundred types of cancerous growth of cells that can affect almost any part of the body including brain, lung, breast, skin, blood, colon or cervix.
Up to 40% of all cancer deaths can be prevented by eliminating tobacco use, improving diets and physical activity, lowering alcohol consumption, eliminating workplace carcinogens and immunizing against Hepatitis B virus and human papillomavirus. Also a large proportion of cancer can be cured if detected early.
Lot of Researches have shown that Curcumin the active ingredient in turmeric has emerged as a potent multimodal cancer-preventing agent. Daily intake of required amount of Curcumin can go a long way in preventing cancer
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.
CR-Submanifolds of a Nearly Hyperbolic Cosymplectic Manifold with Semi-Symmet...iosrjce
We consider a nearly hyperbolic cosymplectic manifold and we study some properties of CRsubmanifolds
of a nearly cosymplectic manifold with a semi-symmetric semi-metric connection. We also obtain
some results on 휉−horizontal and 휉 −vertical CR- submanifolds of a nearly cosymplectic manifold with a semisymmetric
semi-metric connection and study parallel distributions on nearly hyperbolic cosymplectic manifold
with a semi-symmetric semi-metric connection.
Effect of Oil Revenues and Non-Oil Exports on Industrial Production: A Case o...iosrjce
This study aims to examine empirically the effect of oil revenues and non-oil exports on industrial
production in Iran, using secondary data over the period from1961-2010. For empirical analysis after checking
the data for stationarity and co-integration test, the least square method has been used. The empirical results
show positive and statistically significant impacts of explanatory variables of oil revenues and non-oil exports
on industrial production of Iran during the study period. The study found that the relevant macro economic
indicator real GDP have positive and significant effect on industrial production while impact of exchange rate
is found negatively insignificant. Diagnostic tests also indicate that no serial correlation, no heteroskedasticity,
and the residuals are normality distributed.
A Compound Metric for Identification of Fault Prone Modulesiosrjce
IOSR Journal of Computer Engineering (IOSR-JCE) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of computer engineering and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in computer technology. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
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).
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
Edible Bird’s Nest Attenuates Procoagulation Effects of High-Fat Diet in RatsElabscience
Edible bird’s nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its
efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats.
Estudio científico de la UV demuestra los beneficios de consumir arándanos an...Emisor Digital
La investigación, realizada por las académicas de la Escuela de Nutrición y Dietética de la Universidad de Valparaíso Ximena Palma y Samanta Thomas, junto al doctor Gonzalo Cruz, del Centro de Neurobiología y Fisiopatología Integrativa (CENFI) y académico del Instituto de Fisiología de la UV, apuntó a evaluar el manejo de la glucosa posprandial (después de las comidas) y la capacidad antioxidante de los arándanos frescos.
Piper nigrum and Ferula foetida shows Significant Antisecretory and Anti Ulce...BRNSS Publication Hub
In the present study, the gastroprotective mechanism of aqueous extract of Piper nigrum and Ferula foetida (AEPF) was investigated. In the current study AEPF showed significant anti ulcer activity in rats. The antiulcerogenic impact of the AEPF is also associated with its antisecretory action since acid may be a major consideration of the event of ulceration. The current data also clearly demonstrated that 400 mg/kg is more effective than 200 mg/kg and 100 mg/kg dose of AEPF and has shown increased pH and decreased total acidity of gastric fluid. The ulcerogenic effect of cysteamine-induced duodenal ulcers was developed in rats that received cysteamine HCl 400 mg/kg. The exact mechanism of pathological process within the cysteamine-induced peptic ulcer model is not totally known, but hypersecretion of gastric acid, deterioration of mucosal resistance, and promotion of gastric emptying are among the possible mechanisms. In cold restraint stress-induced ulcer model, blood parameters such as glucose, cholesterol, and triglycerides were estimated. The significant increase in blood sugar level was discovered because, beneath nerve-racking conditions, ductless gland secretes corticosterone in man and glucocorticoid in rats. AEPF significantly reduced the elevated serum cholesterol and triglycerides levels, which may be due to inhibition of stimulation of the sympathetic nervous system. Therefore, it could act as a potent therapeutic agent against peptic ulcer disease.
Evaluation of Antiulcer Activity of Extract of Calycophyllum Spruceanum (Bent...gynomark
Objective The objective of the study was to evaluate the antiulcer activity of ethanolic extract of Calycophyllum spruceanum bark. Methodology The ethanol-HCL and pylorus ligation induced models was selected using swiss albino mice and the animals were fasted overnight and then grouped as negative control (0.9% normal saline), standard (omeprazole 30mg/kg), test 1 (CSBE 100mg/kg) and test 2 (CSBE 200mg/kg). The ulcer score, ulcer index and percent ulcer inhibition were determined in ethanol/HCL model. The volume of gastric secretion, pH, total acidity, ulcer index and percent of ulcer inhibition was determined in pylorus ligation model. The ulcerogenic abrasions in the mucosal membrane were observed under a microscope (10X) and scored manually. Results The preliminary phytochemical screening indicated the presence of sterols, alkaloids, glycosides, flavonoids, saponins and coumarins. The bark extract was tolerable at dose of 2000mg/kg. The selected doses of the extracts of 100, 200mg/kg was shown the significant and dose dependent antiulcer activity in ethanol/HCL and pylorus-ligation models as 11.08 %, 32.59% and 28.29%, 37.03% respectively. The dose of 200mg/kg of CSBE was shown the superlative activity ((#p?0.001)) in both models. Conclusion: It was concluded that, the ethanolic extract of Calycophyllum spruceanum bark has a significant antiulcer activity. This activity might be due to presence of supportive phytochemical like flavonoids, alkaloids, steroids. and glycosides. Hence, further evaluation is needed to isolate and identify the specific constituents responsible for the activity.
Similar to Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin-induced gastric ulcers in normal and diabetic rats (20)
An Examination of Effectuation Dimension as Financing Practice of Small and M...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Does Goods and Services Tax (GST) Leads to Indian Economic Development?iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Childhood Factors that influence success in later lifeiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Emotional Intelligence and Work Performance Relationship: A Study on Sales Pe...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Customer’s Acceptance of Internet Banking in Dubaiiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
A Study of Employee Satisfaction relating to Job Security & Working Hours amo...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Consumer Perspectives on Brand Preference: A Choice Based Model Approachiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Student`S Approach towards Social Network Sitesiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Broadcast Management in Nigeria: The systems approach as an imperativeiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
A Study on Retailer’s Perception on Soya Products with Special Reference to T...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
A Study Factors Influence on Organisation Citizenship Behaviour in Corporate ...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Consumers’ Behaviour on Sony Xperia: A Case Study on Bangladeshiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Design of a Balanced Scorecard on Nonprofit Organizations (Study on Yayasan P...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Public Sector Reforms and Outsourcing Services in Nigeria: An Empirical Evalu...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Media Innovations and its Impact on Brand awareness & Considerationiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Customer experience in supermarkets and hypermarkets – A comparative studyiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Social Media and Small Businesses: A Combinational Strategic Approach under t...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Secretarial Performance and the Gender Question (A Study of Selected Tertiary...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Implementation of Quality Management principles at Zimbabwe Open University (...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Organizational Conflicts Management In Selected Organizaions In Lagos State, ...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin-induced gastric ulcers in normal and diabetic rats
1. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS)
e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 14, Issue 12 Ver. IV (Dec. 2015), PP 58-71
www.iosrjournals.org
DOI: 10.9790/0853-141245871 www.iosrjournals.org 58 | Page
Gastroprotective effect of flavonoid quercetin and coenzyme Q10
in indomethacin-induced gastric ulcers in normal and diabetic
rats
Eman F. Khaleel 1,4
, Dalia G. Mostafa 2,4
and Ghada A. Abdel-Aleem 3,5
1
Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
2
Department of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt.
3
Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
4
Department of Medical Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
5
Department of Medical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
Abstract: Various studies have indicated that peptic ulcers occurring during the course of diabetic state are
more severe and often associated with complications such as gastrointestinal bleeding. This study is an attempt
to understand the pathogenesis of indomethacin-induced gastric ulcers occurring during the diabetic state using
suitable markers and its amelioration by quercetin and coenzyme Q10 (CoQ10). In this study, diabetic rats
showed an increase in the gastric mucosal levels of Molandialdehyde (MDA), inducible nitric oxide synthase
(iNOS), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), BAX and p53 and a decrease in the activities of
superoxide dismutase (SOD) as compared to normal control (non-diabetic) rats. There was an increase in
gastric ulcer index and gastric ulcer lesions in diabetic gastric mucosa when compared to the normal control
group. Pre-treatment with quercetin andor CoQ10 to normal groups or diabetic groups which treated by
indomethacin caused a significant decrease in gastric ulcer index, MDA, iNOS, IL-6, TNF-α, BAX and p53 with
concomitant increase in SOD activity when compared with normal and diabetic rats treated with indomethacin
alone. So quercetin and CoQ10 are effective in protection against indomethacin-induced gastric ulcers in
normal and diabetic rats. Our findings could bring new hope for a novel modality of gastric ulcer treatment.
Keywords: Coenzyme Q10, Diabetes Mellitus, Gastric ulcer, Indomethacin, Quercetin.
I. Introduction
Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia resulting from
defective insulin secretion, resistance to insulin action or both. Majority of the diabetic patients suffer from
diabetic nephropathy, retinopathy, cardiomyopathy, neuropathy, however, little attention has been paid to the
incidence and healing rate of peptic ulcer in diabetes [1].
Peptic ulcer is a common disorder of the entire gastrointestinal tract [2]. It occurs mainly in the
stomach and the proximal duodenum. The prevention or cure of peptic ulcer is one of the most important
challenges confronting medicine nowadays, as it is certainly a major human illness affecting nearly 8 to 10 % of
the global population, and of these 5% suffer from gastric ulcers [3].
Increased production of free radicals, inhibition of cell proliferation, infiltration of polymorphonuclear
leukocyte, induction of apoptosis, tumor necrosis factor-α (TNF-α) overexpression, and interleukin-1b (IL-1b)
upregulation are coupled to gastric ulcer etiology [4]. Hence, the mechanism by which gastric ulcers are
produced remains unclear [1].
Gastric ulcer therapy faces nowadays a major drawback because most of the drugs currently available
in the market show limited efficacy against gastric diseases and are often associated with severe side effects [5].
In this context, the use of medicinal plants is in continuous expansion all over the world for the prevention and
treatment of different pathologies [6].
Indomethacin is frequently used and clinically relevant experimental model for the induction of acute
gastric ulcer, its use in the present study was based on the fact that non-steroidal anti-inflammatory drugs are
commonly used worldwide [7].
Indomethacin is known to produce erosions, ulcerative lesions, and petechial bleeding in the mucosa of
stomach as serious side effects [8]. The development of the gastric mucosal lesions induced by indomethacin is
mainly mediated through generation of oxygen free radicals and lipid peroxidation [9] as well as nitric oxide
(NO) through iNOS, leading to oxidative burst, which inflicts endothelial damage [10].
The flavonoid quercetin (3,3’,4’,5,7-pentahydroxyflavone) is one of the most potent antioxidant of
plant origin. It protects the gastrointestinal mucosa from acute lesions induced by various experimental models
and against different necrotic agents, including restraint stress, aspirin [11], indomethacin [12], and ethanol-
induced gastric ulcers [13].
2. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
DOI: 10.9790/0853-141245871 www.iosrjournals.org 59 | Page
The main mechanism of action for the gastroprotective effects of this flavonol are its antioxidant
properties [13].
It has been shown in previous studies that antioxidant agents such as coenzyme Q10 and quercetin have
positive effects in DM [14].
Coenzyme Q10 (ubiquinone) is a naturally occurring compound widely distributed in animals and
humans. An essential role of coenzyme Q10 is as an electron carrier in the mitochondrial respiratory chain.
Moreover, coenzyme Q10 is one of the most important lipophilic antioxidants, and it can also regenerate the
other powerful lipophilic antioxidant, alpha-tocopherol [15], besides replenishment of prostaglandin E2 and
nitric oxide in the gastric mucosa; characters that endorse its potential usefulness against gastric damage [16].
Coenzyme Q10 has been shown to act as a hepatoprotective agent, also affects glucose and lipid
metabolism in vitro and in vivo in monogastric species [17].
The aim of this study is to investigate and compare how the extent of oxidative damage and the
antioxidant capacity in the gastric mucosa of non-diabetic and diabetic rats with induced gastric ulcer by
indomethacin. Also, we investigate the possible protective role of coenzyme Q10 and quercetin.
II. Materials And Methods
2.1 Drugs and chemicals
Indomethacin, Thiobarbituric acid, n-butanol, pyridine, sodium dodecyl sulfate (SDS), acetic acid and
diethyl ether were obtained from Sigma Chemical Co. (St. Louis, MO, USA). Indomethacin was suspended in
2% NaCO3 [18]. All drugs solutions and suspensions were freshly prepared and used. Quercetin (No. Q4951),
CoQ10 (C59H90O4, Cat No. C9538), Evans blue dye (Cat No. 206334) and 2,3,5-triphenyltetrazolium chloride
(TTC, Cat T8877) was purchased from Sigma-Aldrich (St. Louis, MO, USA). CoQ10 was prepared in 1%
aqueous solution of Tween 80 as previously described [19].
2.2 Experimental Animals:
Healthy adult male Wistar albino rats weighing 250 – 300 g and aged 8 weeks obtained from the
animal facility centre of the college of medicine at King Khalid University, Abha, Saudi Arabia were used. They
were housed in plastic cages at a temperature of 23 ± 2°C and 55 ± 15% humidity, with a 12 h light/12 h dark
cycle and fed standard rodent diet and water ad libitum. The rats were fasted overnight before the study. All
experiments performed on laboratory animals in this study followed the “Principles of laboratory animal care”
(NIH Publication No. 85, Rev, 1985).
2.3 Experimental design
60 animals were classified into 2 major groups of control or diabetic rats (each group 30 rats), each of
these 2 groups were further subdivided into five subgroups (each group 6 rats) and treated as follows.
1. Control groups: were either normoglycemic (non-diabetic) or diabetic rats received 1ml normal saline i.p.
2. IND treated groups: were normal or diabetic gastric ulcer induced rats which received normal saline, i.p for
14 days and then received single oral dose of indomethacin (IND, 20 mg/kg).
3. IND+Qur treated rats: were normoglycemic or diabetic rats received i.p dose of Quercetin (50 mgkg) for 14
days and then received a single oral dose of IND.
4. IND+COQ10 treated rats: were normoglycemic or diabetic rats received i.p dose of CoQ10 (20 mgkg) for 14
days and then received a single oral dose of IND.
5. IND+Qur+CoQ10: were normoglycemic or diabetic rats received a concomitant dose of both Qur and
CoQ10 using same doses and routs as above and then received a single oral dose of IND.
CoQ10 and Quercetin doses and mode of administration selected in according to previously published
research which demonstrated a safe and therapeutic effect of Quercetin and Co Q 10 in rats [19, 20].
2.4 Induction of diabetes mellitus
Diabetes mellitus was induced in Wistar rats by single intraperitoneal injection of streptozotocin
(50mg/kg) dissolved in 0.1M-citrate buffer (pH 4.5) after overnight fasting for 12 h. The diabetes was assessed
by determining the blood glucose concentration within 48 hours after injection of streptozotocin. The rats with
blood glucose level above 250 mg/dl were selected for the experimental studies [4, 21].
2.5 IND gastric Ulcer induction
At the end of day 14, the rats were fasted overnight. The rats of the ulcer groups mentioned above were
received an intragastric gavage dose of 20 mg/kg indomethacin dissolved in 2% NaCO3 and brought to a
volume of 1.0 ml with saline (pH 6.8). Indomethacin was administered at 7:30 AM and the animals were placed
in their home cages with free access to food and water. Six hours after indomethacin dosing, the rats were
anesthetized and killed with light diethyl ether, the stomachs were isolated, investigated for gastric lesions and
3. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
DOI: 10.9790/0853-141245871 www.iosrjournals.org 60 | Page
some parts were quickly removed and treated as described below for biochemical, molecular and
histopathological studies.
2.6 Assessment of gastric mucosal lesions
Each stomach was opened along the greater curvature. Then, the stomachs were washed with ice-cold
saline and examined for macroscopical mucosal lesions by an observer unaware of the treatment protocol. The
gastric mucosal lesions were expressed in terms of ulcer index (U.I.) according to Peskar et al. [22] which
depends on the calculation of a lesion index by using of a 0-3 scoring system based on the severity of each
lesion. The severity factor was defined according to the length of the lesions. Severity factor 0 = no lesions; 1 =
lesions < 1 mm length; 2 = lesions 2-4 mm length and 3 = lesions > 4 mm length.
The lesions score for each rat was calculated as the number of lesions in the rat multiplied by their respective
severity factor. The U.I. for each group was taken as the mean lesion score of all the rats in that group.
2.7 Preparing the tissue homogenate
100 mg of the stomach tissues were homogenized separately in 0.1 mole Tris-HCl buffer, pH 7.4 using
a homogenizer at 4°C with a diluting factor of 4. The crude tissue homogenate was then centrifuged at a speed
of 9000 rpm for 15 min in a cold centrifuge and the supernatant was collected and stored at -20°C until analysis
for measuring the levels of Molandialdehyde (MDA), the activities of superoxide dismutase (SOD) and
inducible nitric oxide synthase (iNOS) and levels of inflammatory markers including interleukin-6 (IL-6) and
tumor necrosis factor (TNF-α).
2.8 Oxidative stress assays
Lipid peroxidations in the gastric homogenates were measured by measuring the levels of the
Thiobarbituric Acid Reactive Substances (TBARS) using commercial kits (Cat No. NWK-MD-A01, NWLSS,
Vancouver, Ca) as per manufacturer’s instructions. TBA reacts with Malondialdehyde (MDA) forming an
MDA-TBA2 adducts at 532 nm. In brief, tissue supernatant (50 μL) was added to test tubes containing 2 μL of
butylated hydroxytoluene (BHT) in methanol to prevent oxidation of sample. Next, 50 μL of acid (1 M
phosphoric acid) and 50 μL of TBA solution were added. The tubes were mixed, incubated for 60 min at 60°C
and centrifuged. The supernatant was aliquoted and absorbance measured at 532 nm. TBARS levels were
expressed as nmol/mg protein.
Superoxide dismutase (SOD) activity in gastric homogenates was measured using a commercial kit
(Cat. No. 706002, Cayman Chemical, Ann Arb-or, MI, USA) as per manufacturer’s instructions. Briefly, the kit
uses hypoxanthine and xanthine oxidase to generate superoxide radical that is detected through its reaction with
a tetrazolium salt to form a formazan dye that absorbs at 440 nm. SOD dismutates superoxide to hydrogen
peroxide, resulting in a decrease in the amount of formazan dye and absorbance read at 440 nm. The calculated
SOD activity was expressed as U/mg protein, protein was measured by Bradford method.
2.9 ELISA of inflammatory markers and iNOS
Inducible nitric oxide synthase (iNOS, Cat. No R6663) levels were determined in the gastric
homogenates using special rat ELISA kit purchased from STZ ELISA Company, USA. Levels of TNF-α and IL-
6 in gastric homogenates were determined by ELISA (Cat no. ab46070, Abcam, Cambridge, MA, USA and Cat
No. ELR-IL6-001, RayBio, MO, USA, respectively) as per the manufacturer’s instruction. In brief, 100 μl of
homogenate supernatant was used in the reaction and the intensity of the developed color at 450 nm was directly
proportional to the concentration of TNF-α and IL-6 contained in the samples. Gastric levels of TNF-α and IL-6
levels were expressed as pg/mg protein.
2.10 RNA extraction and RT-PCR
The procedure was optimized for semiquantitative detection using the primer pairs and conditions
described in Table 1. Published sequences of Rt-PCR primers used for the detection of BAX, p53 and β-actin
were used according to the procedure established already in our labs [19]. Total RNA was extracted from the
frozen parts of gastric tissue (30 mg) using an RNeasy Mini Kit (Qiagen Pty. Ltd., Victoria, Australia) according
to manufacturer’s directions. The concentration of total RNA was measured by absorbance at 260 nm using a
UV1240 spectrophotometer (Shimadzu, Kyoto, Japan). The purity was estimated by the 260/280nm absorbance
ratio. Single-strand cDNA synthesis was performed as follows: 30 µl of reverse transcription mixture contained
1 µg of DNase pretreated total RNA, 0.75 µg of oligo d (T) primer, 6 µl of 5x RT buffer, 10 mM dithiothreitol,
0.5 mM deoxynucleotides, 50 U of RNase inhibitor, and 240 U of reverse transcriptase (Invitrogen). The RT
reaction was carried out at 40°C for 70 min followed by heat inactivation at 95°C for 3 min. The tested genes
and the internal control (β-actin) were amplified by Rt-PCR using 2 µl RT products from each sample in a 20 µl
reaction containing Taq polymerase (0.01 U/ml), dNTPs (100 mM), MgCl2 (1.5 mM) and buffer (50 mM Tris-
4. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
DOI: 10.9790/0853-141245871 www.iosrjournals.org 61 | Page
HCl). Rt-PCR reactions consisted of a first denaturing cycle at 97°C for 5 min, followed by a variable number
of cycles of amplification, consisting of denaturation at 96°C for 30 sec, annealing for 30 sec, and extension at
72°C for 1 min. A final extension cycle of 72°C for 15 min was included. Annealing temperature was adjusted
for each target: 60°C for P53 and 55°C for BAX and β-actin. A control reaction without reverse transcriptase
was included for every sample of RNA isolated to verify the absence of contamination. PCR products (10 µl)
were electrophoresed on 2% agarose gels containing 100 ng/ml ethidium bromide, and photographed with a
Polaroid camera under ultraviolet illumination.
2.11 Histological studies
Histological examination of stomach samples was carried out by routine histological procedures.
Tissue fixation was carried out, immediately after the experimental procedure, with 10% neutral buffered
formaldehyde solution (pH 7.0). Processing was carried out as per the schedule for dehydration, clearing and
paraffin infiltration, and then the collected tissue was embedded in paraffin. Finally, 5 μm sections were cut and
mounted on clean glass slides coated with Mayer’s egg albumin.
2.12 Statistical Analysis
Statistical analysis was performed using Graphpad Prism Statistical Software package (version 6). Data
was presented as means with their standard deviations (mean±SD). Normality and homogeneity of the data were
confirmed before ANOVA. Differences among the experimental groups were assessed by one-way ANOVA
followed by Tukey’s test.
III. Results
3.1 Results of gastric specimens of control groups of rats: (Figure 1)
Our results show normal gastric mucosa with no evidence of ulceration in control group (A),
control+IND+CoQ10 group (D) and control+IND+quercetin+CoQ10 group (E). Large hemorrhagic ulcerated
areas of different length were seen in control+IND group (B). Fewer small to moderate ulcers were seen in
control+IND+quercetin (C).
3.2 Assessment of gastric specimens obtained from diabetic group of rats: (Figure 2)
Normal gastric mucosa with no evidence of ulceration was seen in control DM1 group (A) and
DM1+IND+Quercetin+CoQ10 group (E). Large haemorhagic ulcerated areas of different length were seen in
DM1+IND (B). Fewer small to moderate ulcers were seen in DM1+IND+quercetin (C) and DM1+IND+CoQ10
groups (D).
3.3 Results of ulcer index: (Figure 3)
Our results show that there was significant increase in gastric ulcer index in normal+IND and
DM1+INDgroups when compared to control normal and control DM1 groups of rats respectively.
CoQ10 or Quercetin treatment alone or combined treatment of both caused significant decrease in
gastric ulcer index in normal+IND and DM1+IND when compared to control normal or normal+IND groups
and control+IND or DM1+IND.The combined treatment of both CoQ10 and quercetin in DM1+IND caused
more significant decrease in ulcer index when compared to control DM1, DM1+IND, DM1+IND+CoQ10 and
DM1+IND+Quercetin which indicated synergistic effect of both drugs together.
3.4 Results of oxidative stress markers
The levels of MDA, SOD and iNOS were shown in figure (4), figure (5) and figure (6) respectively.
Our results show significant increase in MDA and iNOS with concomitant decrease in SOD in normal+IND and
DM1+IND groups when compared to control normal and control DM1groups.
Treatment with Quercetin or CoQ10 or combined treatment of both in normal+IND or DM1+IND
groups caused significant decrease in MDA and iNOS and significant increase in SOD when compared to
normal+IND or DM1+IND groups. The combined treatment of both quercetin and CoQ10 caused the most
significant decreased in MDA and iNOS and increased in SOD, which indicate synergistic effect of both drugs.
3.5 Results of inflammatory markers
The levels of IL-6 and TNF-α are shown in figure (7) and figure (8) respectively. Our results shows
significant increase in IL-6 and TNF-α in normal+IND and DM1+IND when compared to control normal and
control DM1.There were significant increase in both marker in control DM1 when compared to control normal.
The treatment of normal+IND and DM1+IND with quercetin andor CoQ10 caused significant decreased in IL-6
5. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
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and TNF-α when compared to normal+IND and DM1+IND. The combined treatment of both quercetin and
CoQ10 caused the most significant decreased in their levels.
3.6 Levels of P53 and BAX mRNA
Figure (9) shows semi quantitative reverse transcription PCR product and relative expression of gastric
tissue mRNA P53 and BAX in reference to B actin mRNA. We found that P53 and BAX mRNA in control
normal and DM1were barely detectable. It was noteworthy that the level of P53 mRNA and BAX mRNA
increased in normal+IND group and DM1+IND group. Their levels decreased with treatment with CoQ10
andor quercetin when compared to control+IND or DM1+IND respectively, but still consistently elevated when
compared to normal control or control diabetic. We found that the combined treatment of CoQ10 and quercetn
in normal control+IND and DM1+IND caused the most significant decrease in the levels of P53 mRNA and
BAX mRNA and even though normalized these apoptotic markers.
3.7 Microscopic pictures of gastric tissue obtained from control groups of rats received various form of
treatment: (Figure 10)
Normal gastric mucosa was seen in control normal group (A). Focal sloughing of almost whole
thickness of mucosa surrounded by mild oedema and polymorphonuclear leukocyte (PNL) infiltratration was
seen in normal+IND group (B). Normal+IND+Quercetin group (C) and normal+IND+CoQ10 group (D) show
evidence of very superficial gastric erosion of the mucosa. Almost normal gastric mucosa was seen in
normal+IND+quercetin+Q10 group (E).
3.8 Microscopic pictures of gastric tissue obtained from diabetic groups of rats received various form of
treatment: (Figure11)
Control DM1 group (A) shows normal gastric mucosa.DM1+IND group (B) shows extensive loss of
gastric mucosa and submucosa giving rise to deep ulcer, the floor of which is formed by muscularis propria
.The surrounding gastric mucosa shows evidence of acute inflammatory reaction, hyperemia, edema and atrophy
of some gastric glands .DM1+IND+quercitin (C) and DM1+IND+CoQ10 (D) groups show that the mucosa
shows evidence of superficial ulceration with mild inflammatory reaction comparable to specimen
(B).DM1+IND+Quercetin+CoQ10 group (D) shows almost normal gastric mucosa.
IV. Discussion
Owing to increased rate of diabetes mellitus in human population, related complications like
gastroparesis, intestinal enteropathy have become common. Although the incidence of gastric ulcer in diabetic
patients is paradoxically low, ulcers that occur often become severe leading to gastrointestinal bleeding [4].
In the present study, gastric ulcers in rats were induced by IND, and we studied the gastroprotective
effect of quercetin, CoQ10 and combined quercetin and CoQ10 in normal and type I diabetic rats exposed to
IND-induced gastric ulceration.
We observed the absence of hemorrhagic ulcerative areas by macroscopical examination in control
normal and diabetic rats. Vador et al. [1] found that in normal rats 16 h fasting caused no macroscopic damage
or hemorrhagic lesions whereas, 16 h fasting in diabetic rats caused hemorrhagic gastric lesion in the glandular
part of the stomach. So fasting depletes gastric mucus glycoprotein, and this depletion may be involved in the
pathogenic mechanism of the formation of gastric mucosal lesions [23].
IND is one of NSAIDs have been widely used clinically as anti-inflammatory and analgesic agents. We
observed that administration of IND in normal and diabetic rats caused multiple ulcerations with hemorrhage by
gross examination along with significant increase in gastric ulcer index as compared with control rats. These
results were in agreement with previous studies [9,16,24]. Moreover, these results were confirmed by
histopathological examination of gastric mucosa in IND administered rats which showed necrosis of mucosa,
exposed muscularis mucosa, and congestion of blood vessels.
The study of Konturek et al. [25] demonstrated that the number of stress lesions in diabetes rats were
significantly higher than in non-diabetic rats indicating an increased susceptibility of gastric mucosa to stress
lesions under diabetic conditions.
The study of Owu et al. [24] found that the photomicrographs of the gastric mucosa of normal and
diabetic rats show that parietal cells are irregularly scattered and show some areas of necrosis in diabetic
compared to normal rats. In addition, the epithelial cells appear well defined in the normal but broken and much
more scattered in the diabetic rats. Lesions of the gastric mucosa in diabetes have previously been reported to
include desquamation of the surface epithelium with diffuse and severe hemorrhage with localized erosion [26].
The ulceration induced by IND is attributed mainly to various processes, including generation of
reactive oxygen species, initiation of lipid peroxidation, decreasing the levels of antioxidant parameters,
infiltration of leukocytes, induction of apoptosis, and inhibition of prostaglandin E2 synthesis, nitric oxide level
6. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
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and epithelial cell proliferation in the ulcer margin, which is critical for the reepithelization of the ulcer crater
[27]. Decreased prostaglandin level, due to block of cyclooxygenase (COX) activity, impairs almost all aspects
of gastroprotection as lower mucus and bicarbonate secretion, decreased mucosal blood flow, neutrophil
infiltration, microvascular structural disruption, and increases acid secretions which, in turn, aggravate the ulcer
[28].
Singh et al. [4] speculate that high glucose and ulcerogens treatment generates excessive ROS.
On the other hand, pretreatment of IND-administered to normal and diabetic rats with quercetin or
CoQ10 or combined quercetin and CoQ10 significantly decreased the gastric ulcer index and the number of
ulcers but the effect of CoQ10 was more than quercetin. Among the three treatments tested, co-administration of
quercetin and CoQ10 showed the best effect in reducing the gastric ulcer index. In addition, the combined
treatment had more reducing effect in normal rats compared to diabetic rats.
We also observed the absence of hemorrhagic ulcerative areas by macroscopical examination in
IND+Qur+CoQ10 treated normal and diabetic rats.
In our study we found that diabetes caused a significant increase in the mucosal lipid peroxidation
product (malondialdehyde MDA) levels as compared to normal control (non-diabetic) rats and a significant
decrease in the mucosal antioxidant enzyme levels (SOD). This result is agreement with the study of Vador et
al. [1].
ROS like superoxide radical anions and hydroxyl radicals are now considered one of the major
causative factors for mucosal lesions through oxidative stress. The radicals promote mucosal damage by causing
degradation of the epithelial basement membrane components, complete alteration of the cell metabolism and
DNA damage [29]. GSH and CAT (antioxidant enzymes) scavenges the free radicals, thereby preventing ROS
mediated gastric damage. They also maintain mucosal integrity and were selected as the marker for ROS
mediated gastric damage. Diabetes caused a significant decrease in the GSH and CAT levels. Thus decrease in
the antioxidant enzymes levels is also one of the mechanisms of gastric ulcer formation in diabetes [1].
The study of Vador et al. [1] is the first attempt to understand the pathogenesis of gastric ulcer. They
found an imbalance in the mitochondrial redox state of the cell and lead to excess formation of reactive oxygen
species (ROS). Increased oxidative stress within the cell leads to activation of the poly (ADP-ribose)
polymerase (PARP) pathway, which regulates the expression of genes involved in promoting inflammatory
reactions.
The prevention of oxidative damage in DM by the use of quercetin, a potent antioxidant flavonoid, or
CoQ10 is one of the most important findings of our study. This result is in agreement with Kahraman et al. [13],
Edremitlioğlu et al. [14] and El-Abhar [30].
Quercetin is known to be a potent antioxidant and has been shown to influence enzymes involved in
scavenging reactive oxygen species in vitro and in vivo experiments [31].
The study of Gonzalez-Segovia et al. [32] observed that quercetin administration induced a decrease in
lipid peroxidation in the pyloric antrum of infected animals. This finding could be a result of decreased
neutrophil leukocyte infiltration and free radicals of neutrophil leukocytes in this gastric region. It is also
conceivable that the antioxidant property of quercetin is involved in the decrease of lipid peroxidation, as
suggested by Martín et al. [33] who described a decreased index of lipid peroxidation in gastric injury caused by
ethanol. In these studies no changes were noted in neutrophil leukocyte infiltration.
The possible reason for this could be attributed to antioxidant property of quercetin that protects the
gastric mucosa against oxidative stress associated with diabetes mellitus. Gohlke et al. [34] observed that plasma
glucose level decreased and increased insulin release and insulin sensitivity under quercetin administration.
In El-Abhar [30] study, CoQ10 hindered indomethacin-induced ulcer formation and vascular
permeability, elevated prostaglandin E2, restored the disturbed redox status and boosted nitric oxide level;
however, it failed to increase mucus content significantly.
In fact, CoQ10 in the current work replenished the major antioxidant molecule in the gastric mucosa
that was depleted by indomethacin administration, an effect that is in line with a previous study [16, 30].
Moreover, this ubiquinone has electron donating property that inhibits the decrease in SOD in gastric tissue
(replenish endogenous antioxidants) , hence justifying the preservation of mucosal glutathione levels and
inhibiting lipid peroxidation and thereby stabilizes biological membranes, so it is essential for the health of all
human tissue and organs. Since mucus production, rapid gastric cell turnover, as well as complete barrier
function repair are highly energy dependent processes, thus it is emphasized that adequate energy, besides an
intact mitochondria offered by the higher doses of CoQ10, are needed to combat gastric ulceration [35].
We found that diabetes resulted in a significant increase of plasma IL-6, TNF-α and iNOS levels. This
is agreement with Demir et al. [36] who found that quercetin reduced plasma IL-6 and TNF-α to the levels those
in non-diabetic animals. Therefore, we assumed that quercetin acts as an immunomodulator rather than an
immunosuppressant in diabetic rats.
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Previous study [4] had demonstrated that TNF-α & IL-1b were increased significantly in ulcerated
diabetic gastric tissues compared with non-diabetic.
TNF-α is a proinflammatory cytokine, which induces severe inflammatory reaction leading to gastric
damage. Histopathology of stomach of diabetic rats showed the presence of heavy infiltrates of neutrophils.
Neutrophils have been reported to stimulate TNF-α activity [1].
In addition, we demonstrated that the levels of TNF-α, IL-6 and iNOS increased in diabetic gastric
tissues which were elevated further upon exposure to indomethacin. This result is agreement with Singh et al.
[4] who found that indomethacin upregulated the expression of TNF-α and IL-1β in the gastric tissues of
diabetic rat compared with non-diabetic ones.
It is now well-recognized that the enhanced generation of NO by the iNOS may contribute to the
pathogenesis of various gastroduodenal disorders including peptic ulcer [10]. High concentrations of NO may be
detrimental by promoting inflammation via mucosal swelling and epithelial damage. An increase in iNOS
activity and a decrease in eNOS activity in the gastric mucosa are closely related to the development of gastric
mucosal lesions. Currently we confirmed that the indomethacin-induced gastric ulceration increased the mucosal
iNOS expression, but reduced the eNOS expression in mice. This suggested that the iNOS-mediated NO was
primarily responsible for indomethacin-induced gastric ulceration, caused by indomethacin.
Herein, quercetin & CoQ10 significantly decreased the levels of TNF-α, IL-6 and iNOS during
protection of gastric ulcer.
Quercetin or CoQ10 treatment significantly reduced TNF-α level and thus prevented TNF-α mediated
gastric mucosal damage.
Quercetin has a direct anti-inflammatory property through degradation of the Iκβα factor, preventing
NF-κβ nuclear translocation, as a result of the decreased genetic expression and production of relevant
inflammatory mediators such as TNF-α, IL-1β, IL-6, and IL-8, as suggested by Min et al. [37] and Ruiz et al.
[38].
ROS trigger apoptosis via oxidation of mitochondrial inner membrane phospholipid cardiolipin.
Cardiolipin is essential for maintaining mitochondrial architecture and membrane potential and for providing
support to proteins involved in mitochondrial bioenergetics [39]. Cytochrome c is anchored to the outer surface
of the inner mitochondrial membrane by electrostatic and hydrophobic interactions with cardiolipin. During the
early phase of apoptosis, mitochondrial ROS production is stimulated, and cardiolipin is oxidized. This
destabilizes the interaction with cytochrome c, which then detaches from the membrane and is released into the
cytoplasm through pores in the outer membrane. Cytochrome c release from mitochondria is a key step in the
initiation of apoptosis [40, 41].
In our study, we demonstrated that indomethacin upregulated expressions of BAX and p53 in the
gastric tissues of diabetic rat compared with non-diabetic ones. Quercetin & CoQ10 significantly attenuated
their expressions.
CoQ10 possesses antiapoptotic activity [42] preserving thus gastric epithelial cells that secrete more
mucus hampering gastric ulceration, as indomethacin gastropathy has been previously linked to programmed
cell death [16].
V. Figures And Tables
Figure 1: Assessment of gastric ulcer lesions in the stomachs of Normal groups of rats (A) Control group. (B)
Normal+IND group. (C) Normal+IND+Qur treated rats. (D) Normal+IND+CoQ10 treated rats. (E)
Normal+IND+Qur+CoQ10 treated rats.
8. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
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Figure2: Assessment of gastric ulcer lesions in the stomachs of Diabetic groups of rats (A) Control diabetic
group. (B) DM1+IND group. (C) DM1+IND+Qur treated rats. (D) DM1+IND+CoQ10 treated rats. (E)
DM1+IND+Qur+CoQ10 treated rats.
Figure 3: Ulcer index (UI) of stomachs obtained from all groups of rats. Values are expressed as Mean ± SD for
8 rats in each group. Values were considered significantly different at P < 0.05. a
Significantly different when
compared to control normal group. b
Significantly different when compared to Normal+IND group.
c
Significantly different when compared to Normal+IND+Qur. d
Significantly different when compared to
Normal+IND+CoQ10. m
Significantly different when compared to Normal+IND+Qur+CoQ10. e
Significantly
different when compared to Control DM1. f
Significantly different when compared to DM1+IND. g
Significantly
different when compared to DM1+IND+Qur. h
Significantly different when compared to DM1+IND+CoQ10.
9. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
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Figure 4: Levels of MDA in gastric homogenates of all groups of rats. Values are expressed as Mean ± SD for 8
rats in each group. Values were considered significantly different at P < 0.05. a
Significantly different when
compared to control normal group. b
Significantly different when compared to Normal+IND group.
c
Significantly different when compared to Normal+IND+Qur. d
Significantly different when compared to
Normal+IND+CoQ10. m
Significantly different when compared to Normal+IND+Qur+CoQ10. e
Significantly
different when compared to Control DM1. f
Significantly different when compared to DM1+IND. g
Significantly
different when compared to DM1+IND+Qur. h
Significantly different when compared to DM1+IND+CoQ10.
Figure5: Levels of superoxide dismutase (SOD) in gastric homogenates of all groups of rats. Values are
expressed as Mean ± SD for 8 rats in each group. Values were considered significantly different at P < 0.05.
aSignificantly different when compared to control group. a
Significantly different when compared to control
normal group. b
Significantly different when compared to Normal+IND group. c
Significantly different when
compared to Normal+IND+Qur. d
Significantly different when compared to Normal+IND+CoQ10.
m
Significantly different when compared to Normal+IND+Qur+CoQ10. e
Significantly different when compared
to Control DM1. f
Significantly different when compared to DM1+IND. g
Significantly different when compared
to DM1+IND+Qur. h
Significantly different when compared to DM1+IND+CoQ10.
10. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
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Figure 6: Levels of inducible nitric oxide synthase (iNOS) in gastric homogenates of all groups of rats. Values
are expressed as Mean ± SD for 8 rats in each group. Values were considered significantly different at P < 0.05.
. a
Significantly different when compared to control normal group. b
Significantly different when compared to
Normal+IND group. c
Significantly different when compared to Normal+IND+Qur. d
Significantly different when
compared to Normal+IND+CoQ10. m
Significantly different when compared to Normal+IND+Qur+CoQ10.
e
Significantly different when compared to Control DM1. f
Significantly different when compared to DM1+IND.
g
Significantly different when compared to DM1+IND+Qur. h
Significantly different when compared to
DM1+IND+CoQ10.
Figure 7: Levels of interleukin 6 (IL-6) in gastric homogenates of all groups of rats. Values are expressed as
Mean ± SD for 8 rats in each group. Values were considered significantly different at P < 0.05. a
Significantly
different when compared to control normal group. b
Significantly different when compared to Normal+IND
group. c
Significantly different when compared to Normal+IND+Qur. d
Significantly different when compared to
Normal+IND+CoQ10. m
Significantly different when compared to Normal+IND+Qur+CoQ10. e
Significantly
different when compared to Control DM1. f
Significantly different when compared to DM1+IND. g
Significantly
different when compared to DM1+IND+Qur. h
Significantly different when compared to DM1+IND+CoQ10.
11. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
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TNF-(pg/mg)
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Figure 8: Levels of tumor necrosis factor-α (TNF-α) in gastric homogenates of all groups of rats. Values are
expressed as Mean ± SD for 8 rats in each group. Values were considered significantly different at P < 0.05. .
a
Significantly different when compared to control normal group. b
Significantly different when compared to
Normal+IND group. c
Significantly different when compared to Normal+IND+Qur. d
Significantly different when
compared to Normal+IND+CoQ10. m
Significantly different when compared to Normal+IND+Qur+CoQ10.
e
Significantly different when compared to Control DM1. f
Significantly different when compared to DM1+IND.
g
Significantly different when compared to DM1+IND+Qur. h
Significantly different when compared to
DM1+IND+CoQ10.
Figure 9: Semiquantitative reverse transcription PCR products and relative expression of gastric tissue mRNA
of p53 and BAX in reference to β-actin mRNA (housekeeping gene). The RT-PCR products obtained from all
groups were separated by 2 % agarose gel electrophoresis with 100 ng/ml ethidium bromide. 1: Control normal
group, 2: Normal+IND group. 3: Normal+IND+Qur. 4: Normal+IND+CoQ10. 5: Normal+IND+Qur+CoQ10.
7: Control DM1, 8: DM1+IND group. 9: DM1+IND+Qur. 10: DM1+IND+CoQ10. 11:
DM1+IND+Qur+CoQ10. 6 and 7 are negative control were reverse transcriptase was omitted.
12. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
DOI: 10.9790/0853-141245871 www.iosrjournals.org 69 | Page
Figure 10: Photomicrographs of gastric tissue obtained from the normal groups of rats received vehicle or
various treatments. (A) were taken from Control normal group. (B) was taken from Normal+IND group. (C)
was taken from Normal+IND+Qur. (D) was taken from Normal+IND+CoQ10. (E) was taken from
Normal+IND+Qur+CoQ10. H&E stain (200X)
Figure 11: Photomicrographs of gastric tissue obtained from the Diabetic groups of rats received vehicle or
various treatments. (A) were taken from Control DM1 group. (B) was taken from DM1+IND group. (C) was
taken from DM1+IND+Qur. (D) was taken from DM1+IND+CoQ10. (E) was taken from
DM1+IND+Qur+CoQ10. H&E stain (200X).
13. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin….
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VI. Conclusion
In summary, we documented that gastric ulcers in diabetic rats are severe and we have found that
experimental diabetes aggravates acute indomethacin-induced gastric lesions via mechanism involving an
increase in expression and release of proinflammatory cytokines such as TNF-α and IL-6.
We conclude that quercetin and CoQ10 are effective in protection against indomethacin-induced
gastric ulcers though their actions under diabetic conditions seems to be attenuated, possibly due to reduction in
SOD and increased MDA and the release of proinflammatory cytokines (IL-6 & TNF-α), iNOS and apoptotic
markers (BAX & p53) in diabetic conditions .
Our data demonstrated that treatment with quercetin and CoQ10 can prevent indomethacin-induced
gastric ulceration in rats, by a number of distinct mechanisms. It was found that they can significantly reduce
various inflammatory modulators including IL-6, TNF-α as well as iNOS. These, along with their ability to
strengthen the mucosal defense system by augmenting antioxidants, gastric mucin, and PGE, might be
responsible for the excellent ulcer protection action of quercetin and CoQ10. Treatment with CoQ10 showed
more protection than quercetin. Combined treatment showed complete protection.
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