Protective effects of thymoquinone on streptozotocin-induced diabetic nephropathy

The aim of this study was designed to investigate the possible beneficial effects of the thymoquinone (TQ) in streptozotocine (STZ)-induced diabetes in rats. The rats were randomly allotted into one of three experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with TQ); each group contain ten animals. B and C groups received STZ. Diabetes was induced in two groups by a single intra-peritoneal (i.p) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/l citrate buffer, pH 4.5). Two days after STZ treatment, development of diabetes in two experimental groups was confirmed by measuring blood glucose levels in a tail vein blood samples. Rats with blood glucose levels of 250 mg/dl or higher were considered to be diabetic. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally by using intra gastric intubation for 12 weeks starting 2 days after STZ injection. Treatment of TQ reduced the glomerular size, thickening of capsular, glomerular and tubular basement membranes, increased amounts of mesangial matrix and tubular dilatation and renal function as compared with diabetics untreated. We conclude that TQ therapy causes renal morphologic and functional improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of TQ treatment may indicate its usefulness as a potential treatment in diabetic nephropathy.     

Nephroprotective potential of Quercus infectoria galls against experimentally induced diabetic nephropathy in rats through inhibition of renal oxidative stress and TGF-β

Diabetic nephropathy (DN) is the leading cause of death in diabetic patients and the current treatment options available have a limited significance. The insect galls of Quercus infectoria are traditionally important in the treatment of numerous diseases including diabetes. Hence, the present study was undertaken to evaluate the effect of Q. infectoria gall extract (QIGE) against experimental DN. Type 2 diabetes was induced by feeding rats with a high-fat diet (HFD) initially for 5 weeks, followed by a single intraperitoneal injection of streptozotocin (STZ, 35?mg/kg?bw/day). QIGE was administered to the rats orally at doses of 100 and 200?mg/kg?bw/day, respectively. At the end of the experimental period, various glycemic and renal function parameters were evaluated in the serum, urine and kidney tissues. The QIGE treatment significantly (p?p?via the inhibition of hyperglycemia-induced oxidative stress and renal TGF-β expression and is, therefore, a potential therapeutic agent in the treatment of diabetic complications, especially DN.     

Influence of myrcene on inflammation,matrix accumulation in the kidney tissues of streptozotocin-induced diabetic rat

There is only limited literature studies on the activities of inflammation and matrix accumulation in the renal tissues of rats induced with diabetes through Streptozotocin. The present the investigation involves the examination of the protective actions of Myrcene (MYN), a monoterpene on the oxidative stress, inflammation, and matrix accumulation. For this purpose an experimental setup was created which involves injecting MYN 50 mg/kg for about 45 days in the STZ diabetic rats. Modifications in the enzymes, collagens, growth factor B₁ and Kappa factor P65 were identified and tracked. The levels of the inflammatory markers like TF-α1, ICAM-1, VCAM-1, MCP-1 were tracked and noted. The current experimental results showed an alteration in the glucose metabolism and enhanced condition. Also an increased level of TGF-β-1 and Nuclear factor-kB expression was seen in the renal tissues. MYN was found to reduce glucose oxidative stress and exhibit an anti-inflammatory effect via inhibiting NF-kB signalling. The conclusion of the current study reveals that MYN regulates the inflammatory activities and matrix accumulation by inhibiting the activities of inflammatory cytokine, pro-inflammatory signalling.     

Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy

BackgroundRecently, extract of Ginkgo biloba leaves (GbE) have become widely known phytomedicines and have shown various pharmacological activities, including improvement of blood circulation, protection of oxidative cell damage, prevention of Alzheimer's disease, treatment of cardiovascular disease and diabetes complications. This study was designed to investigate the effects of an ethanolic GbE on renal fibrosis in diabetic nephropathy (DN) and to clarify the possible mechanism by which GbE prevents renal fibrosis.Study designWe investigated the protective effects of GbE on renal fibrosis in STZ-induced diabetic rats. Rats were randomized into six groups termed normal control, diabetes mellitus, low dose of GbE (50 mg/kg/d), intermediate dose of GbE (100 mg/kg/d), high dose of GbE (200 mg/kg/d) and rapamycin (1 mg/kg/d).MethodsAfter 12 weeks, the rats were sacrificed and then fasting blood glucose (FBG), creatinine (Cr), blood urea nitrogen (BUN), urine protein, relative kidney weight, glycogen and collagen accumulation, and collagen IV and laminin expression were measured by different methods. The amounts of E-cadherin, α-SMA and snail, as well as the phosphorylation of Akt, mTOR and p70S6K in the renal cortex of rats, were examined by western blotting.ResultsCompared with diabetic rats, the levels of Cr, BUN, urine protein, relative kidney weight, accumulation of glycogen and collagen, and expression of collagen IV and laminin in the renal cortex were all decreased in GbE treated rats. In addition, GbE reduced the expression of E-cadherin, α-SMA, snail and the phosphorylation of Akt, mTOR and p70S6K in diabetic renal cortex.ConclusionGbE can prevent renal fibrosis in rats with diabetic nephropathy, which is most likely to be associated with its abilities to inhibit the Akt/mTOR signaling pathway.     

Comparative hypoglycemic and nephroprotective effects of tocotrienol rich fraction (TRF) from palm oil and rice bran oil against hyperglycemia induced nephropathy in type 1 diabetic rats

Diabetic nephropathy (DN) is a serious complication confronted by patients with diabetes. Available data indicate that the development of DN is linked to hyperglycemia. Tocotrienol rich fraction (TRF) from palm oil (PO) and rice bran oil (RBO) has been shown to lower the blood glucose level in patients and preclinical animal models. This study was designed to investigate if TRF from PO and RBO could improve the renal function in DN by the virtue of their hypoglycemic and antioxidant activities. Male Wistar rats having an average body weight (bw) 250 g were divided into four groups of six each .The first group served as diabetic control [injected with 55 mg/kg bw of streptozotocin (STZ), intraperitoneally], while the second and third group received PO-TRF and RBO-TRF, respectively, by gavage at a dose of 200 mg/kg bw/day, over a period of 8 weeks post-induction of diabetes. The fourth group comprised of age-matched male Wistar rats that received single intraperitoneal injection of normal saline only and served as control. After 8 weeks of STZ injection and TRF treatment, 24 h urine was collected and animals were sacrificed. Fasting blood glucose, glycosylated hemoglobin, biochemical markers of renal function and oxidative stress were evaluated in serum, urine and kidney tissue. The results show that treatment with PO-TRF as well as RBO-TRF significantly improved the glycemic status and renal function in type 1 diabetic rats but PO-TRF afforded greater efficiency at similar dose as compared to RBO-TRF. In conclusion, PO-TRF was found to be more effective hypoglycemic and nephroprotective agent in DN than RBO-TRF.     

Nephro-protective effect of granulocyte colony-stimulating factor in streptozotocin induced diabetic rats

Diabetic nephropathy is one of the most serious complications of diabetes and the major cause of end-stage renal failure. Consequences of diabetic nephropathy include increased kidney size and glomerular volume, thickening of basement membranes and progressive accumulation of extracellular matrix. Reports in the literature support an association between increased secretion of inflammatory molecules, such as cytokines, growth factors and metalloproteinases, and development of diabetic nephropathy. We investigated the potential of granulocyte colony- stimulating factor (G-CSF) as a therapeutic candidate for preventing diabetic nephropathy. We used 21 8-week-old male rats; 14 were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. The rats were divided into three groups of seven: group 1, control; group 2, diabetic; group 3, diabetic plus G-CSF treatment. After 4 weeks, immunoexpressions of transforming growth factor β1 (TGF-β1), Akt and CD34 levels were measured in the kidney tissue. Blood glucose, urine protein and the glomerular area also were measured for each group. We found that G-CSF treatment decreased TGF-β1 immunoexpression, urine protein and glomerular area in kidneys of diabetic rats, and increased CD 34 and Akt immunoexpression in kidneys of diabetic rats. The effects of G-CSF were independent of blood glucose levels. G-CSF may be a useful therapeutic agent for preventing diabetic nephropathy.     

Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats

Oxidative stress induced by diabetes mellitus leads to damages in the brain, as a consequence of which cognitive functions is impaired. Therefore, for the treatment of diabetes mellitus, in addition to antidiabetics, antioxidants are used to cope with oxidative stress. The antioxidant ability of pomegranate flowers (PGF) to cope with the oxidative stress was investigated. Rats were divided into five groups with 12 animals in each group as given below: control, diabetes (STZ), STZ + the PGF I (300 mg/kg/day), STZ + PGF II (400 mg/kg/day) and STZ + PGF III (500 mg/kg/day).The findings from Morris water maze and probe tests showed that the animals in STZ group had impairments in learning and memory performances compared to the control group. Supplementation of PGF led to improvements in learning and memory performances of diabetic rats.While lipid peroxidation (LPO) was increased (P<0.001), glutathione (GSH) content was decreased (P<0.001) in hippocampal tissue of STZ-induced diabetic rats when compared with control values. Supplementation of PGF restored the levels of LPO and GSH towards their control values. Daily PGF supplementation to diabetic rats reduced the increase in glial-fibrilar acidic protein (GFAP) contents induced by diabetes in the hippocampus, which was significant in STZ + PGF III in comparison to STZ group (p<0.05).In conclusion, these observations suggest that PGF supplementation decreases oxidative stress and ameliorates impairment in learning and memory performances in diabetic rats. Therefore, we suggest that PGF supplementation may be clinically useful in treating neuronal deficit in diabetic patients.     

Effects of Andrographis paniculata (Burm. F.) Extract on Diabetic Nephropathy in Rats

Background:Hyperglycemia and accumulation of advanced glycation end products (AGEs) play a significant role in the development of diabetic nephropathy. Andrographis paniculata (AP) is a plant with high flavonoid content with the potential to suppress oxidative stress activity in cells and tissue. This study was aimed to investigate the role of Andrographis paniculata extract (APE) in protecting kidney damage due to the formation of AGEs in the renal glomerulus in diabetic rats.Methods:A total of 30 male Sprague Dawley rats were randomly divided into five groups as follows: normal control group, streptozocin (STZ) induced diabetic group, STZ-induced diabetic group with AP extract (100 mg/kg BW), STZ-induced diabetic rats with AP extract (200 mg/kg BW), and STZ-induced diabetic rats with APE (400 mg/ kg BW). Blood glucose levels were measured before treatment and after treatment. Serum and urine parameters were determined. Antioxidant enzymes and lipid peroxide levels were determined in the kidney along with histopathological examination.Results:The finding of this study showed that treatment APE at the dose of 200 mg/kg and 400 mg/kg ameliorated kidney hypertrophy index. SOD, catalase, and GSH activities significantly decreased in the kidney of STZ-diabetic rats compared to the normal control rats. Treatment with APE significantly decreased malondialdehyde level at the dose of 200 and 400 mg/kg BW.Conclusion:This study revealed evidence for improving diabetic retinopathy in male rats treated with Andrographis paniculata extract. APE significantly decreased oxidative stress activities in kidney of diabetic rats.Key Words: Andrographis, Diabetic Nephropathies, Streptozocin, Rats, Oxidative Stress     

P2X7 siRNA targeted to the kidneys increases klotho and delays the progression of experimental diabetic nephropathy

Previous studies in our laboratory have suggested that P2X7 could contribute to the progression of diabetic nephropathy and modulated klotho expression. The aim of this study was to investigate if P2X7 receptor is related to the expression of klotho in the onset of diabetic nephropathy in rats. Seven-week-old male Wistar rats weighing 210 g were all uninephrectomized; two-third of the animals were induced to diabetes with 60 mg/kg streptozotocin i.v., and one-third received its vehicle (control rats). At 4th day of the fifth week of the protocol, half of the diabetic rats received a small interfering RNA targeting for P2X7 mRNA, and the other half received its vehicle. Euthanasia was made at the eighth week. Diabetic animals reproduced all classic symptoms of the disease; besides, they showed reduced renal function and low NO bioavailability; also, SOD1, SOD2, and catalase were increased, probably due to the oxidative stress which was elevated in this situation. Metabolic data of diabetic rats did not change by silencing P2X7 receptor. For the other hand, silencing P2X7 was able to contribute to balance oxidative and nitrosative profile, ultimately improving the renal function and increasing plasma and membrane forms of klotho. These findings suggest that the management of P2X7 receptor can benefit the kidneys with diabetic nephropathy. Further studies are needed to show the therapeutic potential of this receptor inhibition to provide a better quality of life for the diabetic patient.

     

Betanin alleviates oxidative stress through the Nrf2 signaling pathway in the liver of STZ-induced diabetic rats

Background

Continuing hyperglycemia causes and exacerbate oxidative stress. Betanin as the principal pigment of red beet root has antioxidant, anti-inflammatory, and anti-diabetic properties. The purpose of this study was to investigate the potency of betanin on antioxidant defense in STZ-induced diabetic rats’ livers.

Methods

STZ at a single dose of 60 mg/kg body weight was intraperitoneally injected and betanin (10, 20, and 40 mg/kg/day) was administered orally for 28 days. Malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC) levels, and the enzyme activity of superoxide dismutase (SOD), catalases and glutathione peroxidases (GPx) were evaluated in the liver. Furthermore, gene expression of Nrf2 and mentioned antioxidant enzymes were measured by Real-time PCR.

Results

Betanin (10 and 20 mg/kg) significantly reduced PC levels and increased antioxidant enzyme activity in diabetic rats compared to the control diabetic group (P?<?0.01). In comparison to the diabetic control group, all studied genes expression in diabetic rats were increased significantly with betanin at doses of 10 and 20 mg/kg (P?<?0.02). The increase in gene expression at 20 mg/kg of betanin was significantly stronger than others (P?<?0.015) except for the catalase (P?=?0.201), that was almost the same. Moreover, treatment of diabetic rats with 20 mg/kg of betanin could significantly increase TAC levels (P?<?0.05) and decrease MDA levels (P?<?0.001) compared to diabetic control group.

Conclusions

Betanin could increase the antioxidant capacity of liver tissue associated with the Nrf2-mediated pathway in a dose-dependent manner.

     

Angiotensin‐Converting Enzyme Inhibition and Angiotensin AT1 Receptor Blockade Downregulate Angiotensin‐Converting Enzyme Expression and Attenuate Renal Injury in Streptozotocin‐Induced Diabetic Rats

Angiotensin‐converting enzyme (ACE) is upregulated in the diabetic kidney and contributes to renal injury. This study investigates the possible beneficial effects of the ACE inhibitor (ACEI), enalapril and the AT1 receptor blocker (ARB), valsartan, on renal ACE expression, renal structure, and function in streptozotocin (STZ)‐induced diabetic rats. Male Wistar rats were allocated into four groups: control, STZ‐diabetic rats, and STZ‐diabetic rats treated with either enalapril (10 mg/kg/day) or valsartan (50 mg/kg/day) for 8 weeks. Enalapril and valsartan reduced renal ACE mRNA and protein expression, Na⁺/K⁺‐ATPase activity, oxidative stress, and serum transforming growth factor‐β1 levels compared to the diabetic group. Both treatments normalized renal nitrate/nitrite levels and ameliorated the observed histopathological changes. In conclusion, ACE downregulation by ACEI and ARB indicates that angiotensin II upregulates ACE through AT1 receptor. Prevention of diabetes‐induced changes in ACE expression and Na⁺/K⁺‐ATPase activity could be a new explanation of the renoprotective effects of ACEIs and ARBs. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:378‐387, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21500     

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.     

Chronic tempol treatment attenuates the renal hemodynamic effects induced by a heme oxygenase inhibitor in streptozotocin diabetic rats

Heme oxygenase-1 (HO-1) is induced by oxidative stress and plays an important role in protecting the kidney from oxidant-mediated damage in the streptozotocin (STZ) rat model of type-1 diabetes mellitus (DM-1). HO-derived metabolites, presumably carbon monoxide (CO), mediate vasodilatory influences in the renal circulation, particularly in conditions linked to elevated HO-1 protein expression or diminished nitric oxide (NO) levels. We tested the hypothesis that diabetes increases oxidative stress and induces HO-1 protein expression, which contributes to regulate renal hemodynamics in conditions of low NO bioavailability. Two weeks after the induction of diabetes with STZ (65 mg/kg iv), Sprague-Dawley rats exhibited higher renal HO-1 protein expression, hyperglycemia, and elevated renal nitrotyrosine levels than control normoglycemic animals. In anesthetized diabetic rats, renal vascular resistance (RVR) was increased, and in vivo cortical NO levels were reduced (P < 0.05) compared with control animals. Acute administration of the HO inhibitor Stannous mesoporphyrin (SnMP; 40 μmol/kg iv) did not alter renal hemodynamics in control rats, but greatly decreased glomerular filtration rate and renal blood flow, markedly increasing RVR in hyperglycemic diabetic rats. Chronic oral treatment with the SOD mimetic tempol prevented the elevation of nitrotyrosine, the HO-1 protein induction, and the increases in RVR induced by SnMP in the diabetic group, without altering basal NO concentrations or RVR. Increasing concentrations of a CO donor (CO-releasing molecule-A1) on pressurized renal interlobar arteries elicited a comparable relaxation in vessels taken from control or diabetic animals. These results suggest that oxidative stress-induced HO-1 exerts vasodilatory actions that partially maintain renal hemodynamics in uncontrolled DM-1.     

Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats

Chromium picolinate is advocated as an anti-diabetic agent for impaired glycemic control. It is a transition metal that exists in various oxidation states and may thereby act as a pro-oxidant. The present study has been designed to examine the effect of chromium picolinate supplementation on hyperglycemia-induced oxidative stress. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight) and chromium was administered orally as chromium picolinate (1 mg/kg body weight) daily for a period of four weeks after the induction of diabetes. As is characteristic of diabetic condition, hyperglycemia was associated with an increase in oxidative stress in liver in terms of increased lipid peroxidation and decreased glutathione levels. The activity of antioxidant enzymes like superoxide dismutase, catalase and glutathione reductase were significantly reduced in liver of diabetic animals. Levels of α-tocopherol and ascorbic acid were found to be considerably lower in plasma of diabetic rats. Chromium picolinate administration on the other hand was found to have beneficial effect in normalizing glucose levels, lipid peroxidation and antioxidant status. The results from the present study demonstrate potential of chromium picolinate to attenuate hyperglycemia-induced oxidative stress in experimental diabetes.     

Grapefruit Derived Flavonoid Naringin Improves Ketoacidosis and Lipid Peroxidation in Type 1 Diabetes Rat Model

BackgroundHypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known.ObjectivesTo investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats.MethodsSprague-Dawley rats divided into 5 groups (n = 7) were orally treated daily with 3.0 ml/kg body weight (BW)/day of distilled water (group 1) or 50 mg/kg BW of naringin (groups 2 and 4, respectively). Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW) twice daily, respectively.ResultsStretozotocin (STZ) only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA), acetoacetate, β-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI), hepatic glycogen content, malondialdehyde, β-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG) compared to the STZ only-treated group.ConclusionsNaringin is not hypoglycemic but ameliorates ketoacidosis and oxidative stress. Naringin supplements could therefore mitigate complications of diabetic ketoacidosis.     

Sodium Tungstate Attenuate Oxidative Stress in Brain Tissue of Streptozotocin-Induced Diabetic Rats

High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms.     

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.     

Determination of Micronutrients and Oxidative Stress Status in the Blood of STZ-Induced Experimental Diabetic Rat Models

This study aims to research the effect of streptozotocin (STZ) at different doses on the serum micronutrients and oxidative stress status in diabetic rat models. Twenty male rats averaged 250 g and 3–4 months old were used as experimental models. They were put in four groups composed of five rats each. Diabetic was induced by administering STZ 55 and 65 mg/kg intraperitonally. The serum micronutrients including minerals and vitamins (Cu, Zn, Mg, Fe, vitamins D, E, and C) and oxidative stress (malondialdehyde, MDA) were determined. Cu, Zn, and Vitamin D3 levels were found to increase significantly in STZ groups (p < 0.005). Retinol levels decreased significantly in STZ groups (p < 0.005). In the groups administered 55 mg/kg STZ ferrum and vitamin C levels were found significantly lower than the other groups (p < 0.005). In the group given 65 mg/kg STZ α-tocopherol levels were highest (p < 0.005) among other groups. There was not any difference between the groups for MDA, Cu/Zn, and Mg. For both doses, oxidative stress status was not significantly affected within 48 h of the application, however, some micronutritents were affected significantly.     

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.