Antihyperglycemic effect of fraxetin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Epidemiological studies have demonstrated that the diabetes mellitus is a serious health burden for both governments and healthcare providers. The present study was hypothesized to evaluate the antihyperglycemic potential of fraxetin by determining the activities of key enzymes of carbohydrate metabolism in streptozotocin (STZ) – induced diabetic rats. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg b.w). Fraxetin was administered to diabetic rats intra gastrically at 20, 40, 80 mg/kg b.w for 30 days. The dose 80 mg/kg b.w, significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as glucokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and hepatic enzymes (aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP)) in the liver tissues of diabetic rats were significantly reverted to near normal levels by the administration of fraxetin. Further, fraxetin administration to diabetic rats improved body weight and hepatic glycogen content demonstrated its antihyperglycemic potential. The present findings suggest that fraxetin may be useful in the treatment of diabetes even though clinical studies to evaluate this possibility may be warranted.     

Enhanced permeability transition explains the reduced calcium uptake in cardiac mitochondria from streptozotocin-induced diabetic rats

Cardiac dysfunction is associated with diabetes. It was previously shown that heart mitochondria from diabetic rats have a reduced calcium accumulation capacity. The objective of this work was to determine whether the reduction in calcium accumulation by cardiac mitochondria from diabetic rats is related to an enhanced susceptibility to induction of the mitochondrial permeability transition. Streptozotocin-induced diabetic rats were used as a model to study the alterations caused by diabetes in the permeability transition, 21 days after streptozotocin administration. Heart mitochondria were isolated to evaluate respiratory parameters and susceptibility to the calcium-dependent permeability transition. Our results show that streptozotocin diabetes facilitates the mitochondrial permeability transition in cardiac mitochondria, resulting in decreased mitochondrial calcium accumulation. We also observed that heart mitochondria from diabetic rats had depressed oxygen consumption during the phosphorylative state. The reduced mitochondrial calcium uptake observed in heart mitochondria from diabetic rats is related to an enhanced susceptibility to the permeability transition rather than to damage to the calcium uptake machinery.     

Influence of olive leaves extract on hepatorenal injury in streptozotocin diabetic rats

Medicinal plants have always been an important source of new alternative effective compounds for human therapy. Currently, there are many of scientific evidences indicate that the medicinal plants contain a lot of hypoglycemic chemical compounds. The purpose of the present study was to determine the influence of olive leaves extract on hepatorenal injury in diabetic male rats. Experimental diabetes was induced by streptozotocin (STZ). The levels of serum glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, total bilirubin, creatinine, blood urea nitrogen, uric acid and malondialdehyde were significantly increased, while the levels of serum superoxide dismutase, glutathione and catalase were statistically decreased in untreated diabetic rats. Moreover, the histopathological examination showed several alterations in the structure of liver and kidney in untreated diabetic rats. Treatments with low dose and high dose of olive leaves extract in diabetic rats showed remarkable reducing and protecting influences of physiological and histopathological alterations. Moreover, the highly treatment efficiency was noted in diabetic rats treated with high dose followed by low dose of olive leaves extract. Additionally, the results of this study proved that the antioxidant activities of olive leaves extract played a vital role against the hepatorenal injury induced by diabetes. Finally, this study indicates to the importance of the use of olive leaves extract as promising alternative and complementary therapeutic agent against diabetes and its complications.     

Effects of the aqueous extract of white tea (Camellia sinensis) in a streptozotocin-induced diabetes model of rats

White tea (WT) is very similar to green tea (GT) but it is exceptionally prepared only from the buds and young tea leaves of Camelia sinensis plant while GT is prepared from the matured tea leaves. The present study was investigated to examine the effects of a 0.5% aqueous extract of WT in a streptozotocin-induced diabetes model of rats. Six-week-old male Sprague-Dawley rats were divided into 3 groups of 6 animals in each group namely: normal control (NC), diabetic control (DBC) and diabetic white tea (DWT). Diabetes was induced by an intraperitoneal injection of streptozotocin (65 mg/kg BW) in DBC and DWT groups except the NC group. After 4 weeks feeding of 0.5% aqueous extracts of WT, the drink intake was significantly (P < 0.05) increased in the DWT group compared to the DBC and NC groups. Blood glucose concentrations were significantly decreased and glucose tolerance ability was significantly improved in the DWT group compared to the DBC group. Liver weight and liver glycogen were significantly increased and serum total cholesterol and LDL-cholesterol were significantly decreased in the DWT group compared to the DBC group. The food intake, body weight gain, serum insulin and fructosamine concentrations were not influenced by the consumption of WT. Data of this study suggest that the 0.5% aqueous extract of WT is effective to reduce most of the diabetes associated abnormalities in a steptozotocin-induced diabetes model of rats.     

The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10 mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β₁ (TGF-β₁) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β₁, as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β₁ and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.     

Effects of gallic acid on brain lipid peroxide and lipid metabolism in streptozotocin-induced diabetic Wistar rats

This study evaluated the protective effects of gallic acid on brain lipid peroxidation products, antioxidant system, and lipids in streptozotocin-induced type II diabetes mellitus. Streptozotocin-induced diabetic rats showed a significant increase in the levels of blood glucose, brain lipid peroxidation products, and lipids and a significant decrease in the activities of brain enzymic antioxidants. Oral treatment with gallic acid (10 mg and 20 mg/kg) for 21 days significantly decreased the levels of blood glucose, brain lipid peroxidation products, and lipids and significantly increased the activities of brain enzymic antioxidants in diabetic rats. Histopathology of brain confirmed the protective effects of gallic acid. Furthermore, in vitro study revealed the free radical scavenging action of gallic acid. Thus, our study shows the beneficial effects of gallic acid on brain metabolism in streptozotocin-induced type II diabetic rats. A diet containing gallic acid may be beneficial to type II diabetic patients.     

Soluble semicarbazide-sensitive amine oxidase (SSAO) activity is related to oxidative stress and subchronic inflammation in streptozotocin-induced diabetic rats

Diabetes is known to increase the risk of Alzheimer's disease (AD) and vascular dementia via oxidative stress and inflammation. There are speculations that SSAO activity might be related to the development of AD. Our aim was to investigate whether changes of soluble SSAO activity, oxidative stress and inflammation markers are related to each other in diabetes. Soluble and tissue-bound SSAO activities (from serum and aorta, respectively) were determined in streptozotocin (STZ)-induced diabetic rats without insulin treatment, receiving insulin once, or twice daily compared to control animals. After three weeks of treatment soluble and tissue-bound SSAO activities (seSSAO and aoSSAO, respectively), serum total antioxidant status (TAS), high sensitivity C-reactive protein (hsCRP), fructose amine levels and routine laboratory parameters were determined. SeSSAO activity significantly increased in the diabetic groups without treatment and receiving insulin once daily, and a marked decrease in aoSSAO activity was seen in all diabetic groups. Increased oxidative stress was correlated with hsCRP elevation, while hsCRP and seSSAO activity were also significantly correlated. In all groups seSSAO and aoSSAO activities were in negative correlation with each other. Our results support the view that poor metabolic control leads to increased oxidative stress, which in turn may cause the elevation of hsCRP levels. Soluble SSAO on the one hand acts as an adhesion molecule - thus possibly being a factor responsible for the late complications of diabetes - and on the other hand, it may contribute to oxidative stress. Our parsimonious conclusion is that there is a relation between the risk factors of AD and vascular dementia (diabetes, oxidative stress and chronic inflammation) and SSAO activity, which may originate from the vessel wall.     

Tissue specific expression and immunohistochemical localization of glutathione S-transferase in streptozotocin induced diabetic rats: modulation by Momordica charantia (karela) extract

In streptozotocin (STZ)-induced diabetes, destruction of pancreatic beta-cell causes an acute shortage of insulin. Increased oxidative stress is believed to be one of the main factors in the etiology and complications of diabetes. In this study we have reported hyperglycemia and glutathione-associated oxidative stress in rats one week after treatment with STZ. In our previous studies, we have reported oxidative stress-related changes in xenobiotic metabolism in tissues from STZ-induced chronic diabetic rats. Here, we demonstrate by immunohistochemistry, that glutathione S-transferase (GST) isoenzymes are differentially expressed in the liver, kidney and testis of diabetic rats. The distribution of GST isoenzymes was found to be tissue- and regio-specific. In addition, we have also shown that treatment with an extract of Momordica charantia (karela), an antidiabetic herb, modulates GST expression in diabetic rats and reverts them to the normal distribution as seen in the tissues of control rats. These results suggest that glutathione metabolism and GST distribution in the tissues of diabetic rats may play an important role in the etiology, pathology and prevention of diabetes.     

Ontogenesis of intestine morphology and intestinal disaccharidases in chickens (Gallus gallus) fed contrasting purified diets

Two groups of growing posthatching Cornish x Rock cross chickens were fed with either a carbohydrate-containing (52.5%) or a carbohydrate-free diet. At 36 days after hatching some of the chicks in each group were shifted to the opposite diet. Chickens fed on a carbohydrate-containing diet grew faster and achieved higher asymptotic masses than chickens fed on a carbohydrate-free diet. Chickens fed on a carbohydrate-free diet had longer intestines and larger intestinal areas than chickens of the same mass fed on a carbohydrate-containing diet. In both groups sucrase and maltase activity (standardized by either intestinal area or mass) increased from day 1 to approximately day 17. After day 17, chickens fed on a carbohydrate-containing diet exhibited 1.8 and 1.9 times higher sucrase and maltase activities per unit intestinal area, respectively, than chickens fed on a carbohydrate-free diet. Analysis of covariance was used to estimate the contribution of sucrase and the sucrase-independent maltases to maltase activity, and to estimate the effect of diet on the sucrase-independent maltases. Sucrase contributed 80% and 75% of the maltase activity in carbohydrate and carbohydrate-free fed chickens, respectively. Chickens shifted from a carbohydrate-free to a carbohydrate diet converged in gross intestinal morphology and intestinal sucrase and maltase levels with carbohydrate-fed chickens within 8 days. Chickens shifted from carbohydrate to carbohydrate-free diets, in contrast, did not show appreciable changes in intestinal length and after 8 days had not reduced levels of sucrase and maltase to those of chickens fed on the carbohydrate-free diet. A comparison of integrated maltase intestinal activity with published data on glucose uptake showed that the ratio of maltose hydrolysis to glucose uptake seemed to be about 7 and to remain relatively invariant during ontogeny. Because so little is known about the interaction between hydrolysis and uptake in vivo, it is difficult to determine if this relatively high ratio represents excess hydrolytic capacity or if it is needed to provide high lumenal glucose concentrations that maximize uptake.Abbreviations m body mass - K _m Michaelis constant - K _m ^* apparent Michaelis constant - GI gastro-intestinal     

Effects of isoeugenol on oxidative stress pathways in normal and streptozotocin-induced diabetic rats.

Because some complications of diabetes mellitus may result from oxidative damage, we investigated the effects of subacute treatment (10mg/kg/day, intraperitoneal [ip], for 14 days) with the antioxidant isoeugenol on the oxidant defense system in normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free radical-detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with isoeugenol reversed diabetic effects on hepatic glutathione peroxidase activity and on oxidized glutathione concentration in brain. Treatment with the lipophilic compound isoeugenol also decreased lipid peroxidation in both liver and heart of normal animals and decreased hepatic oxidized glutathione content in both normal and diabetic rats. Some effects of isoeugenol treatment, such as decreased activity of hepatic superoxide dismutase and glutathione reductase in diabetic rats, were unrelated to the oxidative effects of diabetes. In heart of diabetic animals, isoeugenol treatment resulted in an exacerbation of already elevated activities of catalase. These results indicate that isoeugenol therapy may not reverse diabetic oxidative stress in an overall sense.     

Coconut products alleviate hyperglycaemic,hyperlipidimic and nephropathy indices in streptozotocin-induced diabetic wistar rats

Type 2 diabetes mellitus (T2DM) is a chronic and one of the most common metabolic diseases affecting large proportion of world population. Diabetes-induced changes in lipid and renal parameters are major risk factors contributing to diabetic complications such as diabetic nephropathy and cardiovascular diseases. Due to adverse effects associated with pharmacological intervention in the T2DM treatment, there is an increased interest in the research focussing on identifying novel plant based therapeutic agents. Here we report the effects of various coconut products on diabetic, lipid and renal parameters in streptozotocin (STZ)-induced diabetic rat model. Diabetic rats demonstrated a significant increase in serum glucose, and glycated haemoglobin levels (HbA1c). Lipid parameters including triglycerides, total cholesterol, low density lipoprotein cholesterol (LDL-cholesterol) and very low density lipoprotein cholesterol (VLDL-cholesterol) were found to be significantly increased, while high density lipoprotein cholesterol (HDL-cholesterol) was significantly declined in diabetic rats. Diabetic rats also displayed increased serum and kidney creatinine, urea, and total protein levels and increased urine glucose, urea, albumin and creatinine levels. Contrastingly, treatment with virgin and filtered coconut oils, coconut water and coconut milk resulted in a significant reversal in the levels of above studied parameters in diabetic rats. Further, these coconut products markedly prevented diabetes induced histopathological changes in kidney tissue. Collectively, the data demonstrate the antidiabetic, hypolipidemic and renal protective properties of various coconut products and underscore the importance of regular consumption of plant based medicinal products in the treatment of T2DM and its complications.     

Caffeic acid phenethyl ester ameliorates changes in IGFs secretion and gene expression in streptozotocin-induced diabetic rats

The protective effect of caffeic acid phenethyl ester (CAPE) against diabetes-induced alteration of IGFs protein and gene expression was investigated in serum, liver, heart, and kidney. In the present study, diabetic rats exhibited the decrease of IGF-I content in serum, liver and heart but the increase of that in kidney and CAPE blocked them. Diabetic rats also manifested the increase of IGF-II content in serum, liver, heart, and kidney and CAPE prevented them. CAPE prevented the diabetes-induced decrease of liver IGF-I mRNA and IGF-II mRNA, which is similar to pattern of IGFs mRNA in kidney. Moreover, diabetic rats exhibited the decrease of heart IGF-I mRNA but the increase of IGF-II mRNA and CAPE blocked them. In conclusion, CAPE, in part, prevented diabetes-induced alteration of IGF-I and IGF-II protein and gene expression in liver, heart, and kidney in rats.     

Effects of beta-carotene on oxidative stress in normal and diabetic rats

Increasing interest in the role of oxidative stress and beta-carotene in disease and prevention led us to examine the results of beta-carotene's administration in diabetic rats, a model for high-oxidative stress. In this experiment, amounts of lipid peroxidation, glutathione, and glutathione disulfide, and activity levels of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and gamma-glutamyl transpeptidase were measured in the liver, kidney, and heart of Sprague-Dawley rats with streptozotocin-induced diabetes, and after treatment with 10 mg/kg/day of beta-carotene for 14 days. Beta-carotene treatment resulted in the reversal of the diabetes-induced increase in hepatic and cardiac catalase activity, the decreased levels of glutathione disulfide in the heart, and the increased cardiac and renal levels of lipid peroxidation. Treatment with beta-carotene exacerbated the increased glutathione peroxidase activity in the heart and the decreased catalase activity in the kidneys. In contrast to reduced hepatic glutathione levels in untreated diabetic rats, beta-carotene treatment increased glutathione levels in diabetic rats. Increased hepatic gamma-glutamyl transpeptidase activity in diabetic rats was not reduced by treatment. Thus, beta-carotene therapy for 14 days prevented/reversed some, but not all, diabetes-induced changes in oxidative stress parameters.     

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.     

Effects of combined quercetin and coenzyme Q(10) treatment on oxidative stress in normal and diabetic rats

Reactive oxygen species may be actively involved in the genesis of various pathological states such as ischemia-reperfusion injury, cancer, and diabetes. Our objective was to determine if subacute treatment with combined antioxidants quercetin and coenzyme Q(10) (10 mg/kg/day ip for 14 days) affects the activities of antioxidant enzymes in normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Quercetin treatment raised blood glucose concentrations in normal and diabetic rats, whereas treatment with coenzyme Q(10) did not. Liver, kidney, heart, and brain tissues were excised and the activities of catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and concentrations of oxidized and reduced glutathione were determined. In the liver of diabetic rats, superoxide dismutase, glutathione peroxidase, and levels of both oxidized and reduced glutathione were significantly decreased from the nondiabetic control, and these effects were not reversed when antioxidants were administered. In kidney, glutathione peroxidase activity was significantly elevated in the diabetic rats as compared to nondiabetic rats, and antioxidant treatment did not return the enzyme activity to nondiabetic levels. In heart, catalase activity was increased in diabetic animals and restored to normal levels after combined treatment with quercetin and coenzyme Q(10). Cardiac superoxide dismutase was lower than normal in quercetin- and quercetin + coenzyme Q(10)-treated diabetic rats. There were no adverse effects on oxidative stress markers after treatment with quercetin or coenzyme Q(10) singly or in combination. In spite of the elevation of glucose, quercetin may be effective in reversing some effects of diabetes, but the combination of quercetin + coenzyme Q(10) did not increase effectiveness in reversing effects of diabetes.     

Effect of oral administration of diphenyl diselenide on antioxidant status,and activity of delta aminolevulinic acid dehydratase and isoforms of lactate dehydrogenase,in streptozotocin-induced diabetic rats

Male albino rats with diabetes induced by the administration of streptozotocin (STZ) (45 mg/kg, i.v.) were treated with oral administration of diphenyl diselenide (DPDS) pre-dissolved in soya bean oil. A significant reduction in blood glucose levels was observed in STZ-induced diabetic rats treated with DPDS compared with an untreated STZ diabetic group. The pharmacological effect of DPDS was accompanied by a marked reduction in the level of glycated proteins, and restoration of the observed decreased levels of vitamin C and reduced glutathione (GSH; in liver and kidney tissues) of STZ-treated rats. DPDS also caused a marked reduction in the high levels of thiobarbituric acid reactive substances (TBARS) observed in STZ-induced diabetic group. Finally, the inhibition of catalase, delta aminolevulinic acid dehydratase (e-ALA-D) and isoforms of lactate dehydrogenase (LDH) accompanied by hyperglycemia were prevented by DPDS in all tissues examined. Hence, in comparison with our earlier report, the present findings suggests that, irrespective of the route of administration and the delivery vehicle, DPDS can be considered as an anti-diabetic agent due to its anti-hyperglycemic and antioxidant properties.     

Efficacy of natural diosgenin on cardiovascular risk,insulin secretion,and beta cells in streptozotocin (STZ)-induced diabetic rats

Costus igneus, has been prescribed for the treatment of diabetic mellitus in India for several years. The aim of this study is to investigate the effects of plant derived diosgenin on cardiovascular risk, insulin secretion, and pancreatic composition through electron microscopical studies of normal and diabetic rats. Diosgenin at a dose of 5 or 10 mg/kg per body weight (bw) was orally administered as a single dose per day to diabetic induced rats for a period of 30 days. The effect of diosgenin on blood glucose, HbA1c, PT, APTT, Oxy-LDL, serum lipid profile, electron microscopical studies of pancreas, antioxidant enzymes (in liver, kidney, pancreas) and hepatoprotective enzymes in plasma and liver were measured in normal and diabetic rats. The results showed that fasting blood glucose, PT, APTT, Oxy-LDL, TC, TG, LDL, ALT, AST, ALP, glucose-6-phosphatase, fructose-1,6-bisphosphatase and LPO levels were significantly (p < 0.05) increased, whereas HDL, SOD, CAT, GSH and the glycolytic enzyme glucokinase levels were significantly (p < 0.05) decreased in the diabetes induced rats and these levels were significantly (p < 0.05) reversed back to normal in diabetes induced rats after 30 days of treatment with diosgenin. Electron microscopical studies of the pancreas revealed that the number of beta cells and insulin granules were increased in streptozotocin (STZ) induced diabetic rats after 30 days of treatment with diosgenin. In conclusion, the data obtained from the present study strongly indicate that diosgenin has potential effects on cardiovascular risk, insulin secretion and beta cell regeneration in STZ induced diabetic rats, these results could be useful for new drug development to fight diabetes and its related cardiovascular diseases.     

Ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats

Hyperglycemia is a central trait of diabetes mellitus (DM) and is linked to an increase in free radical generation and oxidative stress in the testes, resulting in testicular tissue damage and male infertility. Synthetic medicines are commonly used to manage diabetes; however, they are costly and associated with adverse effects. As a result, the search for a safer and affordable alternative from medicinal plants that contain antioxidants has become imperative to scavenge free radicals caused by hyperglycaemia, thereby alleviating male reproductive dysfunction. Therefore, the present aimed to investigate the ameliorative effects of Anchomanes difformis aqueous extract against oxidative stress in the testes and epididymis of streptozotocin-induced diabetic male Wistar rats. A total of 64 male Wistar rats (eight weeks old) weighing 180 ± 10 mg/kg were divided into seven groups at random. Type 2 diabetic mellitus (T2DM) was induced by streptozotocin (STZ) and a 10% fructose injection intraperitoneally using 40 mg/kg body weight rats. The levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, and ferric reducing antioxidant (FRAP) as well as 2, 2-diphenyl-1-picrylhydrazyl (DPPH) values were used to establish the testicular oxidative status. It was found that A. difformis extract significantly (p < 0.05) lowered MDA levels in diabetic rats. Both CAT and SOD activity were significantly (p < 0.05) lower following induction of DM and increased (p < 0.05) after treating with A. difformis. The findings of this study show that A. difformis extract could be a promising source of lead compounds for the development of a therapeutic agent to treat male infertility caused by DM complications.     

Upregulation of small GTPase RhoA in the basilar artery from diabetic (mellitus) rats

The goal of this study was to determine whether RhoA, a small GTPase, might be involved in the development of cerebral pathogenesis in diabetes. Male SD rats (n = 120) were divided into six groups: diabetic for 2, 4, 8 weeks, and an age-matched control group. Diabetes was induced by intravenous injection of streptozotocin (50 mg/kg). RhoA mRNA expression in basilar artery was measured by competitive RT-PCR. RhoA mRNA level was significantly increased in 4 weeks (184.1 +/- 28.5%, n = 7) and 8 weeks (218.7 +/- 24.5%, n = 7) after STZ injection compared to the age matched control basilar arteries (P < 0.05). Western blot was used to measure the membrane binding RhoA level to represent the activity of RhoA. We found that RhoA activity was strikingly increased in the diabetic basilar artery (n = 10 in each groups) compared to control basilar artery after STZ injection. Our data demonstrated that there was an upregulation of RhoA in the basilar artery of STZ induced diabetic rats, suggesting that RhoA might be involved in the cerebral vascular pathogenesis during diabetes mellitus.