Oral supplementation of standardized extract of Withania somnifera protects against diabetes-induced testicular oxidative impairments in prepubertal rats

Male reproductive dysfunctions and infertility are the common consequences of overt diabetes. Available evidence support oxidative stress to be the underlying mechanism for the manifestation of testicular complications during diabetes. In the present study, we assessed the attenuating effects of Withania somnifera root extract (WS) on diabetes-induced testicular oxidative disturbances in prepubertal rats. Four-week-old prepubertal rats were assigned into nondiabetic control, streptozotocin (STZ)-treated and STZ?+?WS supplemented (500 mg/kg b.w./d, oral, 15 days) groups. Experimental diabetes was induced by a single intraperitoneal injection of STZ (90 mg/kg b.w). Terminally, all animals were killed, and markers of oxidative stress were determined in the testis cytosol and mitochondrial fraction. Severe hyperglycemia and regression in testis size were apparent in diabetic rats. A decline in antioxidant defenses with subsequent elevation in the generation of reactive oxygen species and lipid peroxidation was discernible in testis cytosol and mitochondria of diabetic prepubertal rats, which was significantly reversed by WS. However, there was partial restoration of glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and 3-beta hydroxysteroid dehydrogenase activities in testis of diabetic prepubertal rats administered with WS. Taken together, data accrued suggest the potential of WS to improve diabetes-induced testicular dysfunctions in prepubertal rats.     

Effects of vitamin E on microsomal Ca(2+) -ATPase activity and calcium levels in streptozotocin-induced diabetic rat kidney

Vitamin E treatment has been found to be beneficial in preventing or reducing diabetic nephropathy. Increased tissue calcium and abnormal microsomal Ca(2+)-ATPase activity have been suggested as contributing factors in the development of diabetic nephropathy. This study was undertaken to test the hypothesis that vitamin E reduces lipid peroxidation and can prevent the abnormalities in microsomal Ca(2+)-ATPase activity and calcium levels in kidney of streptozotocin (STZ)-induced diabetic rats. Male rats were rendered diabetic by a single STZ injection (55 mg x kg(-1) i.p.). After diabetes was verified, diabetic and age-matched control rats were untreated or treated with vitamin E (400-500 IU kg(-1) x day(-1), orally) for 10 weeks. Ca(2+)-ATPase activity and lipid peroxidation (MDA) were determined spectrophotometrically. Blood glucose levels increased approximately five-fold (> 500 mg x dl(-1)) in untreated-diabetic rats but decreased to 340+/-27 mg x dl(-1) in the vitamin E treated-diabetic group. Kidney MDA levels did not significantly change in the diabetic state. However, vitamin E treatment markedly inhibited MDA levels in both control and diabetic animals. Ca(2+)-ATPase activity was 0.483+/-0.008 U l(-1) in the control group and significantly increased to 0.754+/-0.010 U l(-1) in the STZ-diabetic group (p < 0.001). Vitamin E treatment completely prevented the diabetes-induced increase in Ca(2+)-ATPase activity (0.307+/-0.025 U l(-1), p < 0.001) and also reduced the enzyme activity in normal control rats. STZ-diabetes resulted in approximately two-fold increase in total calcium content of kidney. Vitamin E treatment led to a significant reduction in kidney calcium levels of both control and diabetic animals (p < 0.001). Thus, vitamin E treatment can lower blood glucose and lipid peroxidation, which in turn prevents the abnormalities in kidney calcium metabolism of diabetic rats. This study describes a potential biochemical mechanism by which vitamin E supplementation may delay or inhibit the development of cellular damage and nephropathy in diabetes.     

Effects of leptin on oxidative stress in healthy and Streptozotocin-induced diabetic rats

Aims/hypothesis It is generally accepted that oxidative stress is responsible for etiology and complications of diabetes. During uncontrolled Type 1 diabetes, plasma leptin levels rapidly fall. However, it is not known whether diabetes-induced hypoleptinemia has any role in oxidative stress related to uncontrolled Type I diabetes. The present study was designed to examine the effects of leptin treatment on plasma lipid peroxidation and reduced glutathion of normal and streptozotocin(STZ)-induced diabetic rats. Methods Diabetes was induced by single injection of Streptozotocin (55 mg/kg bw). One week after induction of diabetes, rats began 5-day treatment protocol of leptin injections of (0.1 mg/kg bw i.p.) or same volume vehicle. At the end of the 5th day, rats were sacrificed by cardiac puncture under anesthesia and their plasma was taken for plasma leptin, malondialdehyde, and reduced glutathione measurements. Results Plasma leptin levels decreased in STZ-induced diabetic rats while plasma glucose, TBARS, and GSH levels increased. Plasma leptin levels were not affected with leptin treatment in both diabetic and non-diabetic rats. The elevation in plasma TBARS associated with STZ diabetes decreased with leptin treatment. Leptin also increased plasma GSH levels in diabetic rats. In non-diabetic rats, treatment with leptin did not change plasma TBARS and GSH levels. Conclusions/interpretations In conclusion, leptin treatment is able to attenuate lipid peroxidation in STZ-diabetic rats, in the onset of diabetes, by increasing the GSH levels without affecting hyperglycemia and hypoleptinemia.     

Changes in the function and ultrastructure of vessels in the rat model of multiple low dose streptozotocin-induced diabetes

In this study we investigated functional changes in the femoral artery and ultrastructural alterations in mesenteric vessels and capillaries in the rat model of multiple low dose streptozotocin (STZ)-induced diabetes. Participation of oxidative stress in this model of diabetes was established by studying the effect of the pyridoindole antioxidant stobadine (STB) on diabetes-induced impairment. Experimental diabetes was induced by i.v. bolus of STZ (20 mg/kg) given for three consecutive days to male rats. At the 12(th) week following STZ administration, the animals revealed typical signs of diabetes, such as polyphagia, polydypsia and polyuria. There was no weight gain in the diabetic groups throughout the experiment. No exitus occurred in any group. Diabetes was characterised with high levels of plasma glucose, no significant changes in lipid metabolism, decreased serum levels of glutathione, increased serum levels of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAGA), injured endothelial relaxant capacity of the femoral artery and alterations in ultrastructure of mesenteric arteries and capillaries. Antioxidant STB in the dose of 25 mg/kg body weight i.p. (5 times per week) did not influence glucose levels, however, it mitigated biochemical, functional and ultrastructural changes induced by diabetes, suggesting a role of reactive oxygen species in diabetes-induced tissue damage.     

Comparison of vitamin E, L-carnitine and melatonin in ameliorating carbon tetrachloride and diabetes induced hepatic oxidative stress

This study aimed to investigate whether treatments with vitamin E, L-carnitine and melatonin can protect against CCl₄ and diabetes-induced hepatic oxidative stress. Hepatic oxidative stress was performed in rats through 50% v/v carbon tetrachloride (CCl₄) (1 ml/kg/3days, i.p.), and through diabetes mellitus induced by streptozotocin (STZ) (40 mg/kg, i.p.). Vitamin E (100 mg/kg/day, i.p), L-carnitine (300 mg/kg/day, i.p.) and melatonin (10 mg/kg/day, i.p.) were injected for a period of 6 weeks. Thereafter, changes in serum glucose level, liver function tests, hepatic malondialdehyde (MDA) content, hepatic reduced glutathione (GSH) content, hepatic superoxide dismutase (SOD) activity, and serum total antioxidant capacity (TAC) level were evaluated. In CCl₄-induced liver fibrosis, the efficacy order was melatonin > L-carnitine > vitamin E, while in STZ-induced diabetes, the efficacy order was vitamin E ≥ melatonin > L-carnitine. In conclusion, these data indicate that low dose of melatonin is more effective than high doses of vitamin E and L-carnitine in reducing hepatic oxidative stress induced by CCl₄ and diabetes. Moreover, the potent effect of vitamin E in ameliorating diabetes can be linked not only to the antioxidant actions, but also to the superior effect in reducing diabetes-induced hyperglycaemia. Meanwhile, potency of L-carnitine was nearly the same in CCl₄ and diabetes-induced liver damage.     

Effect of cerebrocrast, a new long-acting compound on blood glucose and insulin levels in rats when administered before and after STZ-induced diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by selective destruction of insulin secreting pancreatic islets beta-cells. The formation of cytokines (IL-1beta, IL-6, TNF-alpha, etc.) leads to extensive morphological damage of beta-cells, DNA fragmentation, decrease of glucose oxidation, impaired glucose-insulin secretion and decreased insulin action and proinsulin biosynthesis. We examined the protective effect of a 1,4-dihydropyridine (DHP) derivative cerebrocrast (synthesized in the Latvian Institute of Organic Synthesis) on pancreatic beta-cells in rats possessing diabetes induced with the autoimmunogenic compound streptozotocin (STZ). Cerebrocrast administration at doses of 0.05 and 0.5 mg/kg body weight (p.o.) 1 h or 3 days prior to STZ as well as at 24 and 48 h after STZ administration partially prevented pancreatic beta-cells from the toxic effects of STZ, and delayed the development of hyperglycaemia. Administration of cerebrocrast starting 48 h after STZ-induced diabetes in rats for 3 consecutive days at doses of 0.05 and 0.5 mg/kg body weight (p.o.) significantly decreased blood glucose level, and the effect remained 10 days after the last administration. Moreover, in these rats, cerebrocrast evoked an increase of serum immunoreactive insulin (IRI) level during 7 diabetic days as compared to both the control normal rats and the STZ-induced diabetic control rats. The STZ-induced diabetic rats that received cerebrocrast had a significantly high serum IRI level from the 14th to 21st diabetic days in comparison with the STZ-induced diabetic control.The IRI level in serum as well as the glucose disposal rate were significantly increased after stimulation of pancreatic beta-cells with glucose in normal rats that received cerebrocrast, administered 60 min before glucose. Glucose disposal rate in STZ-induced diabetic rats as a result of cerebrocrast administration was also increased in comparison with STZ-diabetic control rats. Administration of cerebrocrast in combination with insulin intensified the effect of insulin. The hypoglycaemic effect of cerebrocrast primarily can be explained by its immunomodulative properties. Moreover, cerebrocrast can act through extrapancreatic mechanisms that favour the expression of glucose transporters, de novo insulin receptors formation in several cell membranes as well as glucose uptake.     

Attenuation of diabetic nephropathy by tocotrienol: Involvement of NFkB signaling pathway

AimDiabetic nephropathy is a serious complication for patients with diabetes mellitus. Approximately 30–40% of patients with type I and 15% with type II diabetes mellitus develop end stage renal disease. The study was designed to evaluate the impact of tocotrienol on renal function and reno-inflammatory cascade in streptozotocin-induced diabetes.Main methodsStreptozotocin (STZ)-induced diabetic rats were treated with tocotrienol (25, 50 and 100 mg/kg), α-tocopherol (100 mg/kg) or with vehicle form 5th to 8th weeks. After 8 weeks, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. Cytoplasmic and nuclear fractions of kidney was prepared for the quantification of oxidative–nitrosative stress (lipid peroxidation, superoxide dismutase, catalase, non protein thiols, total nitric oxide), tumor necrosis factor-alpha (TNF-α), tissue growth factor-1beta (TGF-β1), p65 subunit of NFκβ and caspase-3.Key findingsAfter 8 weeks of STZ injection, the rats produced significant alteration in renal function, increased oxidative–nitrosative stress, TNF-α, TGF-β1, caspase-3 activity in cytoplasmic lysate and active p65 subunit of NFκβ in nuclear lysate of kidney of diabetic rats. Interestingly, co-administration of tocotrienol significantly and dose-dependently prevented biochemical and molecular changes associated with diabetes. Tocotrienol (100 mg/kg) was demonstrated to be more effective than α-tocopherol (100 mg/kg). Moreover, diabetic rats treated with insulin-tocotrienol combination produced more pronounced effect on molecular parameters as compared to their respective groups.SignificanceTaken together, the data reveal that tocotrienol modulates the release of profibrotic cytokines, oxidative stress, ongoing chronic inflammation and apoptosis and thus exerts a marked renoprotective effect.     

CLOCK/BMAL1 regulates human nocturnin transcription through binding to the E-box of nocturnin promoter

We attempted to clarify the effects of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on nitric oxide synthase (NOS) in streptozotocin-induced diabetic nephropathy. After induction of experimental diabetes with streptozotocin, rats were maintained for 8 weeks with or without treatment by N-hexacosanol (8 mg/kg i.p. every day). Urinary albumin excretion, blood chemistry, immunoblot analysis, and real-time polymerase chain reactions (real-time PCR) of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were investigated. Although N-hexacosanol had no effects on serum glucose or insulin level, it normalized serum creatinine and urinary albumin excretion. N-hexacosanol was found to improve the diabetes-induced alterations in the eNOS, iNOS, and nNOS protein and their mRNA levels. Histologically, N-hexacosanol inhibited the progression to glomerular sclerosis. Our data suggest that N-hexacosanol improves diabetes-induced NOS alterations in the kidney, resulting in the amelioration of diabetic nephropathy.     

The Defensive Effect of Benfotiamine in Sodium Arsenite-Induced Experimental Vascular Endothelial Dysfunction

The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg⁻¹ kg⁻¹ day⁻¹ i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg⁻¹ kg⁻¹ day⁻¹ p.o.) or atorvastatin (30 mg⁻¹ kg⁻¹ day⁻¹ p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-l-arginine methyl ester (L-NAME) (25 mg⁻¹ kg⁻¹ day⁻¹, i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.     

Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin

Berberine (BBR) is one of the main constituents in Rhizoma coptidis and it has widely been used for the treatment of diabetic nephropathy. The aims of the study were to investigate the effects and mechanism of action of berberine on renal damage in diabetic rats. Diabetes and hyperglycaemia were induced in rats by a high-fat diet and intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Rats were randomly divided into 5 groups, such as i) control rats, ii) untreated diabetic rats iii) 250 mg/kg metformin-treated, iv and v) 100 and 200 mg/kg berberine-treated diabetic rats and treated separately for 8 weeks. The fasting blood glucose, insulin, total cholesterol, triglyceride, glycosylated hemoglobin were measured in rats. Kidneys were isolated at the end of the treatment for histology, Western blot analysis and estimation of malonaldehyde (MDA), superoxide dismutase (SOD) and renal advanced glycation endproducts (AGEs). The results revealed that berberine significantly decreased fasting blood glucose, insulin levels, total cholesterol, triglyceride levels, urinary protein excretion, serum creatinine (Scr) and blood urea nitrogen (BUN) in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with berberine. In addition, the protein expressions of nephrin and podocin were significantly increased. It seems likely that in rats berberine exerts an ameliorative effect on renal damage in diabetes induced by high-fat diet and streptozotocin. The possible mechanisms for the renoprotective effects of berberine may be related to inhibition of glycosylation and improvement of antioxidation that in turn upregulate the expressions of renal nephrin and podocin.     

Adenosine triphosphatase activity of streptozotocin-induced diabetic rat brain microsomes. Effect of vitamin E

Hyperglycemia causes protein glycosylation, oxidation and alterations in enzyme activities, which are the underlying causes of diabetic complications. This study was undertaken to test the role of vitamin E treatment on Ca2+-ATPase activity, protein glycosylation and lipid peroxidation in the brain of streptozotocin (STZ)-induced diabetic rats. Male rats weighing about 250-300 g were rendered diabetic by a single STZ injection of 50 mg/kg via the tail vein. Both the diabetic and non-diabetic rats were fed a vitamin E supplemented diet (500 IU/kg/day). Ca2+-ATPase activity was significantly reduced at week 10 of diabetes compared to the control group (p < 0.05), with 0.225+/-0.021 U/I (mean +/- S.E.M.) in the control group and 0.072 +/- 0.008 U/l (mean +/- S.E.M.) in the diabetic group. Vitamin E treatment prevented the enzyme activity from decreasing. The activities observed were 0.226 +/- 0.020 U/l and 0.172 +/- 0.011 U/I (mean +/- S.E.M.) in the vitamin E-treated control and diabetic group, respectively. STZ-induced diabetes resulted in an increased protein glycosylation and lipid peroxidation. Vitamin E treatment led to a significant inhibition in blood glucose, protein glycosylation and lipid peroxidation, which in turn prevented abnormal activity of the enzyme in the brain. This study indicates that vitamin E supplementation may reduce complications of diabetes in the brain.     

The Effect of Boron on Some Biochemical Parameters in Experimental Diabetic Rats

In this study, we evaluated the effect of boron (B) as boric acid (BA) on body weight (b.w.); blood glucose; plasma insulin; lipase and paraoxonase (PON1) activities; and serum triglyceride, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, lipid peroxidation (MDA), and total antioxidant capacity (TAC) in streptozotocin (STZ)-induced experimental diabetes in rats. Sixty Wistar albino rats (200–250 g) were divided into six groups of ten. The groups received the following treatment: group 1, control group; group 2, 50 mg/kg (b.w.) i.p. STZ-induced diabetes; group 3, 5 mg/kg (b.w.) B; group 4, 10 mg/kg (b.w.) B; group 5, diabetes + 5 mg/kg (b.w.) B; and group 6, diabetes + 10 mg/kg (b.w.) B. The experiment lasted 4 weeks. Increased serum MDA levels with diabetes were significantly reduced and although it is not statistically significant, serum TAC levels approached to values of control group; also, insignificant increases were observed in HDL cholesterol levels in experimental diabetic rats with treatment 5 and 10 mg/kg B. Furthermore, body weight, plasma insulin, and lipase activities increased insignificantly, blood glucose and serum LDL cholesterol decreased significantly, and total cholesterol levels decreased insignificantly in the diabetes + 10 mg/kg B group. There was no difference between the groups in terms of plasma PON1 activities and serum triglyceride levels. In conclusion, B may have beneficial effects on some biochemical parameters changes in experimental diabetes, and in order to determine the full effect of this element on the metabolism, further studies are required which use various dosages and compounds of B.     

The effect of thyroid hormones on blood insulin level and metabolic parameters in diabetic rats

The effect of exogenous thyroid hormones on blood insulin and metabolic parameters in diabetic rats was investigated. Three groups of rats were treated with streptozotocin (STZ; 50 mg/kg b.w., intravenously) and one group receiving only saline served as control. Beginning with the third day after STZ treatment, until the last day before decapitation, i.e. for 11 days, two groups of diabetic rats were treated with T3 (50 microg/kg b.w., i.p.) or T4 (250 microg/kg b.w., i.p.). After two weeks, STZ injected rats had lower body weight, hyperglycemia with a simultaneous drop in blood insulin and decrease of T3 and T4 concentrations in comparison to control animals. Liver glycogen content was also reduced, whereas serum lactate, free fatty acids, triglycerides and cholesterol were elevated. Exogenous thyroid hormones given to diabetic rats substantially attenuated hyperglycemia without any significant changes in blood insulin concentration. An additional reduction of body weight gain and depletion in liver glycogen stores were also observed. Thyroid hormones augmented serum lactate and cholesterol and had no beneficial effect on elevated free fatty acids and triglycerides. It can be concluded that in spite of partial restriction of hyperglycemia, thyroid hormones evoked several unfavourable changes strongly limiting their potential use in diabetes.     

Antioxidant role of Umbelliferone in STZ-diabetic rats

The objective of the study was to investigate the role of Umbelliferone (UMB) on lipid peroxidation, nonenzymic and enzymic antioxidants in the plasma and liver of streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180-200 g, were induced diabetes by administration of STZ (40 mg/kg b.wt.) intraperitoneally. The normal and diabetic rats were treated with UMB (30 mg/kg b.wt.) dissolved in 10% dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had an elevation in the levels of lipid peroxidation markers (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD)), and a reduction in nonenzymic antioxidants (vitamin C and reduced glutathione (GSH) except vitamin E in the plasma and liver, and enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the liver. Decreased level of beta-carotene and increased level of ceruloplasmin (Cp) were observed in the plasma of diabetic rats. Treatment with UMB and glibenclamide brought back lipid peroxidation markers, nonenzymic and enzymic antioxidants to near normalcy. Since UMB treatment decreases lipid peroxidation markers and enhances antioxidants' status it can be considered as a potent antioxidant.     

Effects of simvastatin treatment on oxidant/antioxidant state and ultrastructure of streptozotocin-diabetic rat lung

In the present study, we investigated the effects of simvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, on lipid metabolism, lipid peroxidation, antioxidant enzyme activities and ultrastructure of diabetic rat lung. Diabetes was induced by a single injection of streptozotocin (45 mg kg(-1), i.p.). After 8 weeks induction of diabetes, some control and diabetic rats were treated with simvastatin (10 mg kg(-1) rat day(-1); orally) for 4 weeks. Diabetes resulted in significantly high levels of blood glucose and plasma lipids. Malondialdehyde levels were unchanged after 12-week-old diabetic rats, whereas catalase activity significantly decreased in the lung. Glutathione peroxidase activity and nitric oxide level were significantly elevated in the diabetic lung. Histological analysis of the diabetic lung revealed some deterioration in the structure. Simvastatin treatment reduced plasma lipid levels and partially decreased the severity of hyperglycaemia. Catalase, glutathione peroxidase activities and nitric oxide levels were partially restored and accompanied by improved structure in diabetic lung by the simvastatin treatment. These results suggest that structural disturbances and alteration of antioxidative enzyme activities occurred in diabetic lung. Simvastatin treatment may provide some benefits in the maintenance of antioxidant status and structural organization of diabetes-induced injury of lung.     

Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats

We have studied the effects of red wine on brain oxidative stress and nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats with a single intraperitonally injection of STZ (50 mg/kg). Two weeks before and four weeks after injection, red wine was given orally in both normal and diabetic rats. Blood samples were taken from the neck vascular trunk in order to determine the glucose, triglycerides, total cholesterol, HDL-cholesterol (HDL-c), atherogenic index (AI), total protein, blood urea nitrogen (BUN), creatinine, insulin, lipid peroxidation products, reduced glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. As well, we estimated the lipid peroxidtion, GSH and SOD, GSH-Px and catalase activities in brain and renal homogenates, and the excretion of albumin, proteins and glucose in urine over 24 h period. The administration of STZ caused significant increases in levels of glycosuria, proteinuria, albuminuria, glycemia, total cholesterol and AI, as well as in lipid peroxidation products in the brain, plasma and kidney, whereas it decreased the GSH content and SOD, GSH-Px and catalase activities. Treatment with red wine significantly prevented the changes induced by STZ. These data suggested that red wine has a protective effect against brain oxidative stress, diabetic nephropathy and diabetes induced by STZ, as well as it protects against hypercholesterolemia and atherogenic risk.     

Kolaviron,a biflavonoid complex of Garcinia kola seeds modulates apoptosis by suppressing oxidative stress and inflammation in diabetes-induced nephrotoxic rats

Diabetic nephropathy is a complex disease that involves increased production of free radicals which is a strong stimulus for the release of pro-inflammatory factors. We evaluated the renal protective effect of kolaviron (KV) – a Garcinia kola seed extract containing a mixture of 5 flavonoids, in diabetes-induced nephrotoxic rats. Male Wistar rats were divided into 4 groups: untreated controls (C); normal rats treated with kolaviron (C + KV); untreated diabetic rats (D); kolaviron treated diabetic rats (D + KV). A single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) was used for the induction of diabetes. Renal function parameters were estimated in a clinical chemistry analyzer. Markers of oxidative stress in the kidney homogenate were analyzed in a Multiskan Spectrum plate reader and Bio-plex Promagnetic bead-based assays was used for the analysis of inflammatory markers. The effect of kolaviron on diabetes-induced apoptosis was assessed by TUNEL assay. In the diabetic rats, alterations in antioxidant defenses such as an increase in lipid peroxidation, glutathione peroxidase (GPX) activity and a decrease in catalase (CAT) activity, glutathione (GSH) levels and oxygen radical absorbance capacity (ORAC) were observed. There was no difference in superoxide dismutase (SOD) activity. Diabetes induction increased apoptotic cell death and the levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α with no effect on IL-10. Kolaviron treatment of diabetic rats restored the activities of antioxidant enzymes, reduced lipid peroxidation and increased ORAC and GSH concentration in renal tissues. Kolaviron treatment of diabetic rats also suppressed renal IL-1β. The beneficial effects of kolaviron on diabetes-induced kidney injury may be due to its inhibitory action on oxidative stress, IL-1β production and apoptosis.     

Fustin ameliorates hyperglycemia in streptozotocin induced type-2 diabetes via modulating glutathione/Superoxide dismutase/Catalase expressions,suppress lipid peroxidation and regulates histopathological changes

Streptozotocin (STZ) 60 mg/kg, i.p.-induced diabetes in rat’s results into hyperglycemia, impaired oxidative stress, lipid profile, insulin levels and changes in body weight. Treatment with antihyperglycemics and antioxidants are accounted to produce favorable effect in this paradigm. Fustin, a flavonoid derived from Rhus verniciflua, extract of Rhus verniciflua reported to exhibit anti-hyperglycemic, antioxidant, anti-microbial, anti-arthritic effects, anti-obesity effects, antiplatelet effects and anti-cancer effects. However, no evidence is existing on effect of fustin on STZ-induction diabetes. Thus, we evaluated its effects against diabetes in STZ-induced rodents. Blood glucose, Insulin, lipid peroxidation (MDA), superoxide dismutase (SOD), catalase activity (CAT), glutathione (GSH) and lipid profile levels was assessed. After 30 days diabetes induction rodents showed a severe increased blood sugar level, MDA, high density lipid and decreased cholestrol, triglyceride, GSH, SOD, CAT, respectively.Oppositely, treatment with fustin (50–100 mg/kg/p.o., two times daily, 30 days) enhanced blood glucose, lipid profile levels Insulin. Meanwhile, reduced MDA and enhanced GSH, SOD, and CAT in diabetic rats. Glibenclamide 5 mg/kg/p.o. also enhanced diabetes-induced complications and decreased oxidative stress. Further histopathology of pancreas confirms the protective effect fustin in STZ-induction diabetes in animals. In conclusion, the study revealed treatments with fustin avoid the changes in body weight, blood glucose, lipid profile and oxidative stress. As a results of these finding may lead to the growth of a choice of medicine for hyperglycemic in the future.     

金樱子提取液对糖尿病肾病大鼠的肾脏保护作用

目的:研究金樱子提取液对糖尿病肾病(Diabetic Nephropathy,DN)大鼠的肾脏保护作用。方法:在高糖高脂饲料喂食SD(Sprague-Dawley)大白鼠的基础上腹腔注射链脲佐菌素(streptozotocin,STZ)诱导糖尿病肾病大鼠模型,随机分为糖尿病肾病模型组(DN组)和金樱子治疗组(DN+RLM组),同时另设正常对照组(NC组)和金樱子对照组(NC+RLM组)。检测金樱子提取液对各组大鼠血糖(fasting blood-glucose,FBG)、糖化血红蛋白(glycosylated haemoglobin,GHb)、24小时尿微量白蛋白和尿量、血尿素氮(BUN)、血肌酐(Scr)、胆固醇(TC)、甘油三酯(TG)及肾脏结构的影响。结果:与DN大鼠相比,糖尿病肾病大鼠经金樱子提取液治疗后,大鼠FBG、GHb水平、24 h尿微量白蛋白、24 h尿量、肾脏指数明显降低,血脂紊乱、肾功能损害以及DN肾脏病理明显改善,且无明显副作用。结论:金樱子提取液可明显降低DN大鼠血糖,改善DN大鼠血脂、肾功能紊乱及肾脏病理变化,对糖尿病大鼠肾脏具有较强的保护作用。