Kidney Of STZ-induced Diabetic Rats Research Articles

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on oxidative stress and metabolism of elements in kidney of STZ-induced diabetic rats

In diabetes, increased oxidative stress and impaired trace element metabolism play an important role in the pathogenesis of diabetic nephropathy. The objective of this research was to examine the outcomes of blocking the renin-angiotensin system, using either the angiotensin-converting enzyme inhibitor (ACEI), perindopril, or the angiotensin II type 1 (AT1) receptor blocker, irbesartan, on oxidative stress and trace element levels such as Zn, Mg, Cu, and Fe in the kidneys of diabetic rats that had been induced with streptozotocin.Thirty-two Wistar albino male rats were equally divided into four groups. The first group was used as a control. The second group of rats developed diabetes after receiving a single intraperitoneal dose of STZ. The third and fourth groups of rats had STZ-induced diabetes and received daily dosages of irbesartan (15 mg/kg b.w/day) and perindopril (6 mg/kg b.w/day) treatment, respectively.Biochemical analysis of the kidneys showed a distinct increase in oxidative stress, indicated by heightened levels of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activities, as well as reduced glutathione (GSH) levels in the kidneys of diabetic rats. In the kidneys of diabetic rats, the mean levels of Fe and Cu were found to be significantly higher than those of the control group. Additionally, the mean levels of Zn and Mg were significantly lower in the diabetic rats compared to the control rats. Both perindopril and irbesartan decreased significantly MDA content and increased SOD activities and GSH levels in the kidneys of rats with diabetes. The Zn and Mg concentrations in the kidneys of diabetic rats treated with perindopril and irbesartan were markedly higher than in untreated STZ-diabetic rats, while the Cu and Fe concentrations were significantly lower. The urinary excretion of rats treated with perindopril and irbesartan showed a pronounced increase in Cu levels, along with a significant reduction in Zn and Mg levels. Although diabetic rats demonstrated degenerative morphological alterations in their kidneys, both therapies also improved diabetes-induced histopathological modifications in the kidneys.Finally, the present results suggest that manipulating the levels of Zn, Mg, Cu, and Fe - either through ACE inhibition or by blocking AT1 receptors - could be advantageous in reducing lipid peroxidation and increasing antioxidant concentration in the kidneys of diabetic rats.

Antioxidant potential of Hypericum perforatum L. hairy roots extracts in the kidney of STZ-induced diabetic rats

Antioxidant potential of Hypericum perforatum L. hairy roots extracts in the kidney of STZ-induced diabetic rats

The effect of Cinnamomum cassia extract on oxidative stress in the liver and kidney of STZ-induced diabetic rats.

Many diabetes-related complications are caused by oxidative stress. In the current study, the protective effect of Cinnamomum cassia against diabetes-induced liver and kidney oxidative stress was evaluated. The male Wistar rats (n=48) were randomly divided into six groups including; control group received 500µL normal saline orally for 42days. Diabetes groups received intraperitoneally (i.p.) streptozotocin (STZ) as single-dose (60mg/kg, i.p.). Cinnamon extract (100, 200, 400mg/kg) and metformin (300mg/kg) were orally administered to diabetic rats for 42days. After the experiment period, the animals were anesthetized and the liver and kidney tissues were quickly removed and restored for oxidative stress evaluation. The levels of malondialdehyde (MDA), total thiol content, glutathione (GSH), nitric oxide (NO) metabolites, as well as, superoxide dismutase (SOD) and catalase (CAT) activities were measured in kidney and liver tissue. The level of MDA, SOD, and CAT activities increased significantly, while the total thiol content, and NO production were significantly reduced in diabetic animals compared to the control group (from p<0.05 to p<0.001). Treatment with cinnamon extract significantly decreased the MDA level, as well as, SOD and CAT activities in the liver and kidney of diabetic rats (from p<0.05 to p<0.001). In the liver and kidney of cinnamon treated groups, GSH and total thiol contents and NO production were significantly higher than diabetic group (from p<0.05 to p<0.001). Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications.

Effect of Artemisia absinthium ethanolic extract on oxidative stress markers and the TLR4, S100A4, Bax and Bcl-2 genes expression in the kidney of STZ-induced diabetic rats.

The present study was conducted to examine antidiabetic effects of Artemisia absinthium ethanolic extract [A.absinthium] and to investigate its effects on oxidative stress markers and the expression of TLR4, S100A4, Bax and Bcl-2 genes in the kidney of STZ-induced diabetic rats. Thirty six rats (weight 200-250g) were randomly divided into diabetes and control groups. Induction of diabetes was performed using STZ (55mg/kg.bw). Biochemical parameters and oxidative stress markers (SOD and MDA) were measured using spectrophotometry after 60days of treatment. The expression of TLR4, S100A4, Bax and Bcl-2 were analyzed by real-time PCR. One-way analysis of variance (ANOVA) and Bonferroni post hoc test were used to compare the data. Diabetes significantly impairs the serum fasting blood glucose (FBG), lipid profile, urea, creatinine and albumin. At the end of treatment with A.absinthium extract, these parameters were close to the normal range. The results showed that the A.absinthium extract significantly decreased the kidney expression of TLR4, S100A4, Bax and increased the expression of Bcl-2 and improved oxidative stress markers (SOD and MDA) in the kidney tissues of treated rats. Also, all of these beneficial effects of the A.absinthium were dose-dependent. The extract of A.absinthium possesses antidiabetic effects. A.absinthium decreased the expression of TLR4, S100A4, Bax and increased the expression of Bcl-2 and improved oxidative stress. Therefore, this herbal extract can be used as an adjuvant treatment for diabetic complications.

Possible ameliorative role of green tea on chronic alcohol mediated renal toxicity of STZ -induced diabetic rats

Summary This research was planned to assess the protective effect of aqueous green tea extract (AGTE) in alcohol treated diabetic rats. This study was examined, whether 20% v/v of 5 g/kg.b.w alcohol intake exacerbates diabetes-induced renal damage associated with an escalated nitroxidative stress and glucose homeostasis in comparison with diabetic condition alone. The present study is primarily focused to investigate the possible toxic effects of chronic alcohol intake on kidney of streptozotocin (STZ)-induced diabetic rats. Forty albino male Wistar rats were used and randomly allocated into five groups. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg) in rats. Alcohol was administered through orogastric tube once daily for a period of 60 days. Impact of chronic alcohol treatment on renal function and selected metabolites of catecholamines and antioxidant metabolisms have been investigated in the kidney of STZ-induced diabetic rats. Biochemical analysis of kidneys demonstrated that chronic alcohol induced alterations in vitro gluconeogenesis, significant decrease in the body weight, and activities of antioxidant enzymes in diabetic rats. A significant increase in the levels of epinephrine and sertonine was observed between alcohol treated, diabetic control and alcohol treated diabetic rat groups. Further, excessive chronic alcohol treatment caused additive deterioration of the kidney function as evidenced by increased inducible nitric oxide synthase (iNOS) protein expression and thus nitroxidative stress and histopathological aberrations leading to aggravation of diabetic nephropathy under alcohol intoxication. Treatment with aqueous green tea extract (300 mg/kg.b.w) to diabetic rats treated with alcohol renders the protection against the decreased body weight, increased hyperglycemia, hyperlipidemia, catecholamines, nitroxidative stress and further tissue damage.

Protective effects of Croton hookeri on streptozotocin-induced diabetic nephropathy

In this study, the protective effects of Croton hookeri (CH) extract on renal injury were investigated in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single injection of STZ (45 mg/kg) to Sprague-Dawley rats. After 5 days, CH extract (200 mg/kg) was administered daily by oral gavage for 2 weeks. Administration of CH extracts significantly reduced blood glucose levels in STZ-induced diabetic rats. STZ-induced changes in total cholesterol, LDL, HDL, ALT, AST, BUN, and serum creatinine levels were significantly restored by treatment with CH extract. Abnormal levels of SOD, catalase, glutathione, and oxidized GSH (GSSG) in STZ-treated rats were also significantly recovered by CH extract treatment. CH extract markedly reduced the expression of collagen-1, fibronectin, and α-SMA in the kidney of STZ-induced diabetic rats. In particular, oxidative DNA damages, MDA, TGF-β, IL-1β, and IL-6 levels were significantly reduced in STZ-treated rats following treatment with CH extract, whereas IL-10 showed opposite trend. STZ-induced SIRT1, SIRT3 downregulation and cloudin-1 upregulation in the kidney were dramatically recovered by CH extract treatment. Our data suggest that CH extract protects against diabetic-induced nephropathy by inhibiting oxidative stress and inflammation. Therefore, it has potential as a food supplement to alleviate renal dysfunction caused by diabetes-induced nephropathy.

RNA-seq analysis of glycosylation related gene expression in STZ-induced diabetic rat kidney inner medulla.

The UT-A1 urea transporter is crucial to the kidney's ability to generate concentrated urine. Native UT-A1 from kidney inner medulla (IM) is a heavily glycosylated protein with two glycosylation forms of 97 and 117 kDa. In diabetes, UT-A1 protein abundance, particularly the 117 kD isoform, is significantly increased corresponding to an increased urea permeability in perfused IM collecting ducts, which plays an important role in preventing the osmotic diuresis caused by glucosuria. However, how the glycan carbohydrate structure change and the glycan related enzymes regulate kidney urea transport activity, particularly under diabetic condition, is largely unknown. In this study, using sugar-specific binding lectins, we found that the carbohydrate structure of UT-A1 is changed with increased amounts of sialic acid, fucose, and increased glycan branching under diabetic conditions. These changes were accompanied by altered UT-A1 association with the galectin proteins, β-galactoside glycan binding proteins. To explore the molecular basis of the alterations of glycan structures, the highly sensitive next generation sequencing (NGS) technology, Illumina RNA-seq, was employed to analyze genes involved in the process of UT-A1 glycosylation using streptozotocin (STZ)—induced diabetic rat kidney. Differential gene expression analysis combining with quantitative PCR revealed that expression of a number of important glycosylation related genes were changed under diabetic conditions. These genes include the glycosyltransferase genes Mgat4a, the sialylation enzymes St3gal1 and St3gal4 and glycan binding protein galectin-3, -5, -8, and -9. In contrast, although highly expressed in kidney IM, the glycosyltransferase genes Mgat1, Mgat2, and fucosyltransferase Fut8, did not show any changes. Conclusions: In diabetes, not only is UT-A1 protein abundance increased but the protein's glycan structure is also significantly changed. UT-A1 protein becomes highly sialylated, fucosylated and branched. Consistently, a number of crucial glycosylation related genes are changed under diabetic conditions. The alteration of these genes may contribute to changes in the UT-A1 glycan structure and therefore modulate kidney urea transport activity and alleviate osmotic diuresis caused by glucosuria in diabetes.

Selective therapeutic effect of cornus officinalis fruits on the damage of different organs in STZ-induced diabetic rats.

The aim of the present study was to identify the selective therapeutic effects of Corni Fructus (Cornus officinalis Sieb. et Zucc.) on different organs in streptozotocin (STZ)-induced diabetic rats. Diabetes in rats was induced by intraperitonal injection with STZ at a dose of 30 mg/kg body weight (bw) for 3 days (once per a day). STZ-induced diabetic rats were orally administrated Corni Fructus (CF) extract at 300 mg/kg or metformin at 250 mg/kg daily for 4 weeks. Blood glucose and triglyceride (TG) in sera and urine total volume were measured. Histopathological changes of different organs, pancreas, liver, kidney, and lung tissues were observed by H&E staining. The expression of insulin and α-smooth muscle actin (α-SMA) was investigated in pancreas, and kidney by immunohistochemistry, respectively. The results revealed that CF extract significantly decreased the serum levels of blood glucose, and TG, and also urine total volume in STZ-induced diabetic rats. The histological examinations revealed amelioration of diabetes-induced pancreas injury including pathological changes of the Langerhans's islet and glomerular with their loss after the administration of CF extraction. Moreover, the administration of CF extract increased the numbers of insulin releasing beta cells in pancreas and also inhibited the expression of α-SMA in kidney of STZ-induced diabetic rats. On the other hand, CF extract showed no effect on the pathological damages of liver and lung in STZ-induced diabetic rats. These results demonstrated that CF extract may have a selective therapeutic potential through the control of hyperglycemia, and the protection of pancreas and kidney against diabetic damage.

The effects of Syzygium aromaticum-derived oleanolic acid on reactive oxygen species in the heart, liver and kidney of STZ-induced diabetic rats

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Berberine ameliorates renal injury by regulating G proteins-AC- cAMP signaling in diabetic rats with nephropathy

Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to glomerulus and glomerular mesangial cells (MCs) proliferation play a critical role in the pathogenesis of DN. The current studies were undertaken to investigate the protective effects and the possible molecular mechanism of berberine on streptozotocin (STZ)-induced DN rats. Male Wistar rats were randomly assigned to normal control and DN groups of comparable age. Three DN groups received 50, 100 and 200 mg/kg of berberine for 8 weeks via daily intragastrically, respectively. The G proteins-adenylyl cyclase (AC)-cAMP signaling pathway and glomerular MCs proliferation were examined in STZ-induced diabetic rat kidney. Enhanced MCs proliferation and remarkable renal injury were concomitant with activation of Gαi and inhibition of Gαs and cAMP in DN model group. Berberine treatment for 8 weeks abolished the above changes by upregulating the expression of Gαs protein and downregulating the expression of Gαi protein, increasing cAMP level, and inhibiting MCs proliferation compared with model group. Taken together, for the first time, these results demonstrated that berberine can relieve renal injury in DN rats through mediating G proteins-AC-cAMP signaling pathway and inhibiting the abnormal proliferation of MCs by increasing cAMP level, suggesting that berberine could be a potential therapeutic agent for the treatment of DN.

Enhanced downregulation of AT1b receptors on afferent and efferent arterioles in STZ-induced diabetic rat kidney

Enhanced downregulation of AT1b receptors on afferent and efferent arterioles in STZ-induced diabetic rat kidney

Evaluation of trace elements and oxidative stress levels in the liver and kidney of streptozotocin-induced experimental diabetic rat model

In this study, we aimed to investigate the relationship among trace elements (Cu, Fe, Zn and Mg) on oxidative and anti-oxidative substances in liver and kidneys tissues in streptozotocin (STZ) diabetic rat model. The mean levels of Fe and Cu were found significantly higher in the liver and kidneys of the diabetic rats, in comparison to the control rats. On the other hand, the mean levels of Zn and Mg in the liver and kidneys of the diabetic rats were significantly lower than in the control rats. The liver and kidneys malonaldehyde (MDA) levels of the experimental group were found to be higher than in the control group (p < 0.001; p < 0.01, respectively) after 4 weeks of the experimental period. Superoxide dismutase (SOD) activities and glutathione (GSH) levels in the liver tissue of STZ-induced diabetic rats were found to be lower in the experimental group than in the control group (p < 0.01). SOD activity and GSH concentration in kidneys of the diabetic rats were significantly diminished with respect to the control group (p < 0.01). In conclusion, the present results indicate that the increase of Fe and Cu together with decreas of Zn and Mg concentration in liver and kidney of STZ-induced diabetic rats may be involved in disturbances of oxidative balance in both the tissues. Therefore, these findings may contribute to explain the role of impaired ion metabolism of some elements in the progression of diabetic oxidative complications.

Effect of Pimpinellatirupatiensison Oxidative Enzymes in STZ-induced Diabetic Rat Kidney.

The present study was aimed to evaluate the therapeutic potential of Pimpinellatirupatiensis(Pt) by assaying the activities of selective mitochondrial enzymes in streptozotocin induced diabetic rats. Diabetic rats showed a significant (p < 0.01) reduction in the activities of oxidative enzymes Succinate dehydrogenase (SDH), Malate dehydrogenase (MDH), Glutamate dehydrogenase (GDH) and isocitrate dehydrogenase (ICDH). Lactate dehydrogenase (LDH) activity was significantly (p < 0.01) increased in diabetic rats. The daily oral treatment of Pimpinellatirupatiensisethyl alcohol extract (750 mg/kg body weight/day) to diabetic rats for 30 days reversed the above changes in a significant (p < 0.01) manner. From our observations, we conclude that administration of Pt altered the activities of oxidative enzymes, thereby suggesting its role in mitochondrial energy production. The obtained results were compared with Glibenclamide, a standard anti diabetic drug. Thus, the modulatory effects of Pt on altering these enzymes activities afford a promise for widespread use for treatment of diabetes in the future.

Early protective effect of mitofusion 2 overexpression in STZ-induced diabetic rat kidney

Diabetic nephropathy (DN) is a serious complication of diabetes with a poorly defined etiology and limited treatment options. Early intervention is key to preventing the progression of DN. Mitofusin 2 (Mfn2) regulates mitochondrial morphology and signaling, and is involved in the pathogenesis of numerous diseases. Furthermore, Mfn2 is also closely associated with the development of diabetes, but its functional roles in the diabetic kidney remain unknown. This study investigated the effect of Mfn2 at an early stage of DN. Mfn2 was overexpressed by adenovirus-mediated gene transfer in streptozotocin-induced diabetic rats. Clinical parameters (proteinuria, albumin/creatinine ratio), pathological changes, ultra-microstructural changes in nephrons, expression of collagen IV and phosph-p38, ROS production, mitochondrial function, and apoptosis were evaluated and compared with diabetic rats expressing control levels of Mfn2. Endogenous Mfn2 expression decreased with time in DN. Compared to the blank transfection control group, overexpression of Mfn2 decreased kidney weight relative to body weight, reduced proteinuria and ACR, and improved pathological changes typical of the diabetic kidney, like enlargement of glomeruli, accumulation of ECM, and thickening of the basement membrane. In addition, Mfn2 overexpression inhibited activation of p38, and the accumulation of ROS; prevented mitochondrial dysfunction; and reduced the synthesis of collagen IV, but did not affect apoptosis of kidney cells. This study demonstrates that Mfn2 overexpression can attenuate pathological changes in the kidneys of diabetic rats. Further studies are needed to clarify the underlying mechanism of this protective function. Mfn2 might be a potential therapeutic target for the treatment of early stage DN.

The influence of rutin on the extracellular matrix in streptozotocin-induced diabetic rat kidney

We previously reported that rutin administration to streptozotocin (STZ)-induced diabetic rats decreased plasma glucose and increased plasma insulin levels. In this study, we have examined the role of rutin on matrix remodelling in the kidney of STZ-induced diabetic rats. STZ was administered intraperitoneally (50 mg kg(-1)) to male albino Wistar rats to induce experimental diabetes. Rutin (100 mg kg(-1)) was orally administered to normal and STZ-induced diabetic rats for a period of 45 days and its influence on the content of hydroxyproline and collagen and on the activity of matrix metalloproteinases (MMPs) were studied. We have also studied the levels of tissue inhibitors of metalloproteinases (TIMPs) in the kidney. STZ-induced diabetic control rats showed increased content of hydroxyproline and collagen, decreased activity of MMPs and increased levels of TIMPs in the kidney. These changes were positively modulated by rutin treatment in STZ-induced diabetic rats, thereby protecting the kidney. In normal rats treated with rutin, none of the parameters studied were significantly altered. From the results obtained, we could conclude that rutin influences MMPs and effectively protects kidney against STZ-induced damage in rats. The effects observed are due to the reduction of plasma glucose levels by rutin.

Effects of Green Tea on Matrix Metalloproteinases in Streptozotocin-induced Diabetic Rats

Matrix metalloproteinases (MMPs) are considered to be important for cardiovascular disease and nearly associated with the loss of renal function by diabetes mellitus. Green tea catechins inhibit mRNA expression and activity of MMPs in vitro study. We investigated in vivo study whether oral green tea administration could cause a change of MMPs in diabetic rats. Experimental diabetes was induced by single injection of 50 mg/kg streptozotocin (STZ) via the tail vein. The diabetic rats were fed on a green tea-free diet or 5% green tea-containing diet for four weeks. After four weeks, green tea ingestion significantly decreased the HbA1c level in STZ-induced diabetic rats (STZ rats). The activities of MMP-2 and MMP-9 in plasma determined by zymography significantly increased in diabetic rats compared with those of control rats, though both activities showed no change by green tea ingestion. The mRNA expression of MMP-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in rat whole kidney, was determined by RT-PCR. The mRNA expression of MMP-9 and TIMP-1 significantly decreased in diabetic rat kidney compared with control rat, but green tea ingestion in diabetic rats (STZ+GT rats) allowed both expressions to recover to control level. MMP-2 and TIMP-2 mRNA expression in STZ+GT rats significantly increased compared with control rats and STZ rats. Thus, feeding with 5% green tea-containing diet improved the impairment of MMP regulation in STZ-induced diabetic rat kidney.

KOBALT KULLANIMININ STZ-DENEYSEL DİYABETİK SIÇANLARIN BÖBREK DOKULARINDA CAT, GSH-PX, SOD AKTİVİTELERİ VE LİPİD PEROKSİDASYONU DÜZEYLERİNE ETKİSİ

It has been stated that free radicals cause several complications in diabetics. Several researches until now showed that, trace elements play an important role in formation of free radicals. On the other hand, it is claimed that cobalt has a blood glucose lowering effect. From this point of view, in streptozotocin (STZ) induced diabetic rats were given cobalt (II) chloride (0,5 mM), kidney samples were taken from each group at the 2nd, 4th and 6th weeks and the activities of catalase, glutathione peroxidase, superoxide dismu.tase and levels of TBARS were analysed. In STZ-induced diabetic rat kidney, it has been indicated that there was a decrease in the catalase, glutathione peroxidase and superoxide dismutase activities of the tissues upon administration. Moreover, cobalt also reduced TBARS levels which are increased in diabetes. As a result, we believe that at the early stage of diabetes, the cobalt dose which was used in this study can be considered as appropriate as regards regulation of oxidative and antioxidative systems.