Antidiabetic activity of levan polysaccharide in alloxan-induced diabetic rats

This study aims to examine the effects of polysaccharide levan on oxidative stress and hyperglycemia in alloxan-induced diabetic rats. Levan, used in this study, was a microbial levan synthetisized by a non pathogenic bacteria recently isolated and identified as Bacillus licheniformis. Animals were allocated into four groups of six rats each: a control group (Control), diabetic group (Diab.), normal rats received levan (L) and diabetic rats fed with levan (DL). Treated diabetic rats were administrated with levan in drinking water through oral gavage for 60 days. The administration of polysaccharide levan in diabetic rats caused a significant increase in glycogen level by 52% and a decrease in glucose level in plasma by 52%. Similarly, the administration of polysaccharide levan in diabetic rats caused a decrease in the thiobarbituric acid-reactive substances (TBARS) by 31%, 41%, 39% and 25%, an increase in superoxide dismutase (SOD) by 40%, 50%, 44% and 34%, and in catalase (CAT) by 18%, 20%, 12% and 18% in liver, kidney, pancreas and heart, respectively. Furthermore, a significant decrease in hepatic and renal indices toxicity was observed, i.e. alkalines phosphatases (ALP), aspartate and lactate transaminases (AST and ALT) activities, total bilirubin, creatinine and urea levels by 19%, 31%, 32%, 36%, 37% and 23%, respectively. The results show that administration of polysaccharide levan can restore abnormal oxidative indice near normal levels. This study demonstrates, for the first time, that polysaccharide levan is efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggests that levan supplemented to diet may be helpful in preventing diabetic complications in adult rats.     

Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in vitro and in rats

This study aimed to evaluate the effect of phenolic extract and purified hydroxytyrosol (HT) from olive mill waste (OMW) on oxidative stress and hyperglycemia in alloxan-induced diabetic rats. The OMW biophenols were extracted using ethyl acetate. The obtained extract was fractionated by solid phase extraction (SPE) experimentation to generate two fractions: (F1) and (F2). HPLC-UV and HPLC-MS analysis showed that (F1) was made of known OMW monomeric phenolics mainly hydroxytyrosol (HT) while (F2) contained oligomeric and polymeric phenols such as verbascosid and ligstrosid. (HT) was purified from (F1) using silica gel-column chromatography and silica gel-TLC techniques. In incubated pancreas, supplementation of OMW fractions enhanced insulin secretion. The administration of OMW extract fractions (F1) and (F2) as well as purified (HT) in diabetic rats caused a decrease in glucose level in plasma and an increase in renal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities in liver and kidney. Furthermore, a protective action against hepatic and renal toxicity in diabetic rats was clearly observed. Furthermore, a significant decrease in hepatic and renal indices toxicity was observed, i.e. alkalines phosphatases (ALP), aspartate and lactate transaminases (AST and ALT) activities and the thiobarbituric acid-reactive substances (TBARs), total and direct bilirubin, creatinine and urea levels. In addition, (F1), (F2) and especially (HT) decreased triglycerides (TG), total-cholesterol (T-Ch) and higher HDL-cholesterol (HDL-Ch) in serum. These beneficial effects of OMW biophenols were confirmed by histological findings in hepatic, renal and pancreatic tissues of diabetic rats. This study demonstrates for the first time that OMW polyphenols and especially (HT) are efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggests that administration of HT may be helpful in the prevention of diabetic complications associated with oxidative stress.     

Hypolipidemic effect of diet supplementation with bacterial levan in cholesterol-fed rats

Levan polysaccharide, a type of fructan, has been shown to have industrial applications as a new industrial gum in the fields of cosmetics, foods like dietary fiber and pharmaceutical goods. The objective of this current study was to investigate the possible hypolipidemic and antioxidative effects of levan in rats fed with a high-cholesterol diet. Animals were allocated into four groups of six rats each: a normal diet group (Control), normal rats received levan (L), a high-cholesterol diet group (Chol) and a high-cholesterol diet with a daily dose of levan equivalent to 5%. Treated hypercholesterolemic rats were administrated with levan in drinking water through oral gavage for 60 days. After the treatment period, the plasma antioxidant enzymes and lipid profiles were determined. Our results show that treatment with levan polysaccharide positively changed plasma antioxidant enzyme activities and lipid profiles (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides) in cholesterol-rats, and thus may have potential hypolipidemic and antioxidant effects. Levan could protect against oxidative stress linked atherosclerosis and decrease the atherogenic index.     

Hyperglycaemia, stress oxidant, liver dysfunction and histological changes in diabetic male rat pancreas and liver: protective effect of 17 beta-estradiol

Oxidative stress is thought to play a crucial role in the pathogenesis of chronic diabetic complications. We investigated the protective effects of 17 beta-estradiol (E2) on alloxan-induced stress oxidant, hepatic dysfunction and histological changes in male rats liver and pancreas. Our results showed that 17 beta-estradiol could attenuate the increase of blood glucose in plasma and normalise the hepatic glycogen level. In addition, E2 enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) (by 207, 52 and 72%, respectively, as compared to diabetic rats), reduced lipid peroxidation in the hepatic tissue (by 54%) and improved the liver dysfunction parameters by the significant decrease of gamma-glytamyl transferase (GGT), phosphatases alkalines (PAL), lactate deshydrogenase (LDH) and aspartate and lactate transaminases (AST and ALT) activities which increased in diabetic rats. Moreover, 17 beta-estradiol treatment in diabetic rats protects against alloxan-induced pancreatic beta-cells and hepatic cells damages.     

Ameliorative effect of 20-OH ecdysone on streptozotocin induced oxidative stress and β-cell damage in experimental hyperglycemic rats

The present study was to evaluate the effects of 20-OH ecdysone on hyperglycemia mediated oxidative stress in streptozotocin induced diabetic rats. Diabetes was induced in experimental rats by single intraperitoneal injection of STZ (45 mg/kg b.w.) dissolved in 0.1 mol/L citrate buffer (pH 4.5). Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of non-enzymic antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic rats. Moreover, hepatic markers (aspartate aminotransferase and alanine aminotransferase) and renal markers (urea, creatinine) were significantly increased in diabetic rats as compared to control rats. Upon treatment with 20-OH ecdysone to diabetic rats showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that 20-OH ecdysone exerts a protective action on pancreatic beta cell function and overcomes oxidative stress through its hypoglycemic potential. The effect produced by the 20-OH ecdysone on various parameters was comparable to that of glibenclamide – an antidiabetic drug.     

Therapeutic effects of stem cell on hyperglycemia,hyperlipidemia, and oxidative stress in alloxan-treated rats

Diabetes mellitus is the most common endocrine disorder that affects more than 285 million people worldwide. The purpose of this study was to investigate the effect of mesenchymal stem cells (MSCs) from the bone marrow of albino rats, on hyperglycemia, hyperlipidemia, and oxidative stress induced by intraperitoneal injection (i.p.) of alloxan at a dose of 150 mg/kg in rats. Injection of alloxan into rats resulted in a significant increase in serum glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, and sialic acid level and a significant decrease in serum insulin, high density lipoprotein-cholesterol, vitamin E, and liver glycogen as compared to their corresponding controls. Also, oxidative stress was noticed in pancreatic tissue as evidenced by a significant decrease in glutathione level, superoxide dismutase, glutathione-S-transferase activities, also a significant increase in malondialdehyde and nitric oxide levels when compared to control group. Treatment of diabetic rats with MSCs stem cells significantly prevented these alterations and attenuated alloxan-induced oxidative stress. In conclusion, rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats. This may be helpful in the prevention of diabetic complications associated with oxidative stress.     

Augmentation of hepatic and renal oxidative stress and disrupted glucose homeostasis by monocrotophos in streptozotocin-induced diabetic rats

Several recent studies have demonstrated that organophosphorus insecticides (OPI) possess the potential to disrupt glucose homeostasis leading to hyperglycemia in experimental animals. The propensity of OPI to induce hyperglycemia along with oxidative stress may have far-reaching consequences on diabetic outcomes and associated complications. The primary objective of this study was to assess the potential of monocrotophos (MCP), an extensively used OPI, on hepatic and renal oxidative stress markers and dysregulation of hepatic glucose homeostasis in experimentally induced diabetic rats. Rats rendered diabetic by a single dose of streptozotocin (60 mg/kg b.w) were orally administered MCP (0.9 mg/kg b.w/d for 5 d). Monocrotophos per se caused only a marginal increase in blood glucose levels but significantly elevated the blood glucose levels and also disrupted glucose homeostasis by depleting liver glycogen content and increasing the gluconeogenetic enzyme activities in diabetic rats. Experimentally induced diabetes was also associated with alterations in antioxidant enzymes in liver and kidney. MCP markedly enhanced lipid peroxidation in kidney and altered the enzymatic antioxidant defense mechanisms in both liver and kidney of diabetic rats. Collectively our data provides evidence that MCP has the propensity to augment the oxidative stress and further disrupt glucose homeostasis in diabetic rats.     

Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats

The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.     

Resveratrol attenuates hyperglycemia-mediated oxidative stress,proinflammatory cytokines and protects hepatocytes ultrastructure in streptozotocin–nicotinamide-induced experimental diabetic rats

The present study was hypothesized to investigate the hepatoprotective nature of resveratrol in averting hyperglycemia-mediated oxidative stress by measuring extent of oxidant stress and levels of proinflammatory cytokines and antioxidant competence in the hepatic tissues of streptozotocin–nicotinamide-induced diabetic rats. After the experimental period of 30 days, the pathophysiological markers such as serum bilirubin and hepatic aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were studied in addition to hepatic TNF-α, IL-1β, IL-6, NF-κB p65 and nitric oxide (NO) levels in control and experimental groups of rats. The levels of vitamin C, vitamin E and reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) were determined in the liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides, hydroperoxides and protein carbonyls. A portion of liver was processed for histological and ultrastructural studies. Oral administration of resveratrol (5 mg/kg b.w.) to diabetic rats showed a significant decline in hepatic proinflammatory cytokines and notable attenuation in hepatic lipid peroxides, hydroperoxides and protein carbonyls. The diminished activities of hepatic enzymic antioxidants as well as the decreased levels of hepatic non-enzymic antioxidants of diabetic rats were reverted to near normalcy by resveratrol administration. Moreover, the histological and ultrastructural observations evidenced that resveratrol effectively rescues the hepatocytes from hyperglycemia-mediated oxidative damage without affecting its cellular function and structural integrity. The findings of the present investigation demonstrated the hepatocyte protective nature of resveratrol by attenuating markers of hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic tissues of diabetic rats.     

Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.     

Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats

The present study aimed to investigate the potential effects of vitamins (C and E)/melatonin co-administration on the hematologic and hepatic functions and oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood glucose levels (hyperglycemia) associated with serious hematologic disorders (P?<?0.01) evidenced by the decrease in the levels of red blood cell count (RBC) (?18 %), hematocrit (Ht) (?18 %), hemoglobin content (Hb) (?36 %), mean corpuscular hemoglobin (MCH) (?17 %), and mean corpuscular hemoglobin concentration (MCHC) (?16 %). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and the plasmatic levels of total cholesterol and triglyceride contents of diabetic rats were, however, noted to undergo significant increases by 42 % (P?<?0.01), 134 % (P?<?0.001), 27.5 % (P?<?0.01), 147 % (P?<?0.001), and 67 % (P?<?0.01), respectively, as compared to the control animals. Furthermore, a significant increase in malondialdehyde (MDA) content and a significant decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were observed in the plasma and hepatic tissues of diabetic rats when compared to the controls. Interestingly, the treatment with vitamins (C, E) in combination with melatonin was noted to reduce the plasma levels of glucose, lower the MDA levels, and restore the hematologic parameters and biochemical and antioxidant levels of diabetic rats back to normal values, alleviating diabetes metabolic disorders in rats.     

Protective effects of either C-peptide or l-arginine on pancreatic β-cell function,proliferation, and oxidative stress in streptozotocin-induced diabetic rats

Diabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C-peptide or l -arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1—control nondiabetic, 2—diabetic (no treatment), 3—diabetic + C-peptide, and 4—diabetic + l -arginine. Diabetes was induced by a single intraperitoneal injection of high dose streptozotocin. At the end of the experiment, sera glucose, insulin levels, total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and pancreatic MDA, TAC, and B-cell lymphoma 2 were measured. The morphology and proliferating activity of the pancreas were examined by hematoxylin and eosin histological stain, proliferative cell nuclear antigen (PCNA), and insulin antibodies. Our results showed that induction of diabetes caused hyperglycemia, dyslipidemia, and oxidative stress. However, administration of C-peptide or l -arginine significantly improved the pancreatic histopathology with a significant increase in the area % of insulin immunoreactivity, the number of PCNA immunopositive cells, the number of islets, and the diameter of islets compared with the diabetic group. C-peptide treatment of the diabetic rats completely corrected these errors, while l -arginine partially antagonized the above diabetic complications. So the administration of C-peptide as an adjuvant therapy in type 1 diabetes can significantly decrease apoptosis of pancreas and subsequent progression of diabetes complication.     

Thymoquinone ameliorates chemical induced oxidative stress and β-cell damage in experimental hyperglycemic rats

The present study was aimed to investigate the effect of thymoquinone (TQ) on pancreatic insulin levels, tissue antioxidant and lipid peroxidation (LPO) status in streptozotocin (STZ) nicotinamide (NA) induced diabetic rats. Diabetes was induced in experimental rats by a single intraperitoneal (i.p) injection of STZ (45 mg/kg b.w) dissolved in 0.1 mol/L citrate buffer (pH 4.5), 15 min after the i.p administration of NA (110 mg/kg b.w). Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of low-molecular weight antioxidants Vitamin C, Vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of lipid peroxidation markers were observed in liver and kidney tissues of diabetic control rats as compared to control rats. In addition, diabetic rats showed an obvious decrease in pancreatic insulin levels. Administration of TQ (80 mg/kg b.w) to diabetic rats for 45 days significantly reversed the damage associated with diabetes. Biochemical findings were supported by histological studies. These results indicated that TQ exerts a protective action on pancreatic beta cell function and overcomes oxidative stress through its antioxidant properties.     

Therapeutic Potential of Clove Essential Oil in Diabetes: Modulation of Pro-Inflammatory Mediators,Oxidative Stress and Metabolic Enzyme Activities

Type 1 diabetes is characterized by insulin deficiency due to the destruction of pancreatic β cells, leading to hyperglycemia, which in turn induces vascular complications. In the current study, we investigated the effect of intraperitoneal administration of clove essential oil (CEO: 20 mg/kg body weight) on certain oxidative stress and glucose metabolism enzymes, as well as the expression of proinflammatory mediators. Administration of CEO to diabetic rats showed a significant decline in blood glucose levels, total cholesterol, and xanthine oxidase, compared to the streptozotocin group. Furthermore, these treated rats elicited a notable attenuation in the levels of lipid peroxides, and thiols groups in both liver and brain tissues. The activities of antioxidant and metabolic enzymes were reverted to normality in diabetic upon CEO administration. In addition to its protective effects on red blood cell hemolysis, CEO is a potent α-amylase inhibitor with an IC₅₀=298.0±2.75 μg/mL. Also, treatment of diabetic rats with CEO significantly reduced the iNOS expression in the spleen. Our data showed that CEO has potential beneficial effects on diabetes, which can possibly prevent the pathogenesis of diabetic micro- and macrovascular complications.     

Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats

Diabetes mellitus is the most common serious metabolic disorder and it is considered to be one of the five leading causes of death in the world. Hyperglycemia-mediated oxidative stress plays a crucial role in diabetic complications. Hence, this study was undertaken to evaluate the protective effect of esculetin on the plasma glucose, insulin levels, tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. Extent of oxidative stress was assessed by the elevation in the levels of lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD); reduction in the enzymic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST); nonenzymic antioxidants Vitamin C, E and reduced glutathione (GSH) were observed in the liver and kidney tissues of diabetic control rats as compared to control rats. Oral supplementation of esculetin to diabetic rats for 45 days significantly brought back lipid peroxidation markers, enzymic and nonenzymic antioxidants to near normalcy. Moreover, the histological observations evidenced that esculetin effectively rescues the hepatocytes and kidney from hyperglycemia mediated oxidative damage without affecting its cellular function and structural integrity. These findings suggest that esculetin (40 mg/kg BW) treatment exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic and renal tissues. Further, detailed studies are in progress to elucidate the molecular mechanism by which esculetin elicits its modulatory effects in insulin signaling pathway.     

The Protective Effect of Vanadium Against Diabetic Cataracts in Diabetic Rat Model

The present study was designed to investigate the effect of vanadium in alloxan-induced diabetes and cataract in rats. Different doses of vanadium was administered once daily for 8 weeks to alloxan-induced diabetic rats. To know the mechanism of action of vanadium, lens malondialdehyde (MDA), protein carbonyl content, activity of superoxide dismutase (SOD), activities of aldose reductase (AR), and sorbitol levels were assayed, respectively. Supplementation of vanadium to alloxan-induced diabetic rats decreased the blood glucose levels due to hyperglycemia, inhibited the AR activity, and delayed cataract progression in a dose-dependent manner. The observed beneficial effects may be attributed to polyol pathway activation but not decreased oxidative stress. Overall, the results of this study demonstrate that vanadium could effectively reduce the alloxan-induced hyperglycemia and diabetic cataracts in rats.     

Effect of Eugenia Jambolana seed kernel on antioxidant defense system in streptozotocin-induced diabetes in rats

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. The aim of this study was to investigate the effect of ethanolic extract of Eugenia jambolana seed kernel on antioxidant defense systems of plasma and pancreas in streptozotocin-induced diabetes in rats. The levels of glucose, vitamin-C, vitamin-E, ceruloplasmin, reduced glutathione and lipidperoxides were estimated in plasma of control and experimental groups of rats. The levels of lipidperoxides, reduced glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were assayed in pancreatic tissue of control and experimental groups of rats. A significant increase in the levels of plasma glucose, vitamin-E, ceruloplasmin, lipid peroxides and a concomitant decrease in the levels of vitamin-C, reduced glutathione were observed in diabetic rats. The activities of pancreatic antioxidant enzymes were altered in diabetic rats. These alterations were reverted back to near normal level after the treatment with Eugenia jambolana seed kernel and glibenclamide. Histopathological studies also revealed that the protective effect of Eugenia jambolana seed kernel on pancreatic beta-cells. The present study shows that Eugenia jambolana seed kernel decreased oxidative stress in diabetic rats, which inturn may be due to its hypoglycemic property.     

Modulation of xenobiotic metabolism and oxidative stress in chronic streptozotocin-induced diabetic rats fed with Momordica charantia fruit extract

We studied the long-term effects of streptozotocin-induced diabetes on tissue-specific cytochrome P450 (CYP) and glutathione-dependent (GSH-dependent) xenobiotic metabolism in rats. In addition, we also studied the effect of antidiabetic Momordica charantia (karela) fruit-extract feeding on the modulation of xenobiotic metabolism and oxidative stress in rats with diabetes. Our results have indicated an increase (35-50%) in CYP4A-dependent lauric acid hydroxylation in liver, kidney, and brain of diabetic rats. About a two-fold increase in CYP2E-dependent hepatic aniline hydroxylation and a 90-100% increase in CYP1A-dependent ethoxycoumarin-O-deethylase activities in kidney and brain were also observed. A significant increase (80%) in aminopyrene N-demethylase activity was observed only in rat kidney, and a decrease was observed in the liver and brain of diabetic rats. A significant increase (77%) in NADPH-dependent lipid peroxidation (LPO) in kidney of diabetic rats was also observed. On the other hand, a decrease in hepatic LPO was seen during chronic diabetes. During diabetes an increased expression of CYP1A1, CYP2E1, and CYP4A1 isoenzymes was also seen by Western blot analysis. Karela-juice feeding modulates the enzyme expression and catalytic activities in a tissue- and isoenzyme-specific manner. A marked decrease (65%) in hepatic GSH content and glutathione S-transferase (GST) activity and an increase (about two-fold) in brain GSH and GST activity was observed in diabetic rats. On the other hand, renal GST was markedly reduced, and GSH content was moderately higher than that of control rats. Western blot analyses using specific antibodies have confirmed the tissue-specific alterations in the expression of GST isoenzymes. Karela-juice feeding, in general, reversed the effect of chronic diabetes on the modulation of both P450-dependent monooxygenase activities and GSH-dependent oxidative stress related LPO and GST activities. These results have suggested that the modulation of xenobiotic metabolism and oxidative stress in various tissues may be related to altered metabolism of endogenous substrates and hormonal status during diabetes. The findings may have significant implications in elucidating the therapeutic use of antidiabetic drugs and management of Type 1 diabetes in chronic diabetic patients.     

Curcuminoids modulates oxidative damage and mitochondrial dysfunction in diabetic rat brain

Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage and mitochondrial dysfunction. The aim of the present study is to investigate the effects of curcuminoids, polyphenols of Curcuma longa (L.) on oxidative stress and mitochondrial impairment in the brain of streptozotocin (STZ)-induced diabetic rats. A marked increase in lipid peroxidation and nitrite levels with simultaneous decrease in endogenous antioxidant marker enzymes was observed in the diabetic rat brain, which was restored to normal levels on curcuminoids treatment. Down-regulation of mitochondrial complex I and IV activity caused by STZ induction was also up-regulated on oral administration of curcuminoids. Moreover, curcuminoids administration profoundly elevated the ATP level, which was earlier reduced in the diabetic brain. These results suggest that curcuminoids exhibit a protective effect by accelerating antioxidant defense mechanisms and attenuating mitochondrial dysfunction in the brain of diabetic rats. Curcuminoids thus may be used as a promising therapeutic agent in preventing and/or delaying the progression of diabetic complications in the brain.