Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus we aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.     

Nordihydroguairetic acid, a lignin, prevents oxidative stress and the development of diabetic nephropathy in rats

Recent evidences indicate a pivotal role of reactive oxygen species in etiology of diabetic nephropathy, an important microvascular complication of diabetes mellitus. Moreover, oxidative stress leads to an increased production of lipoxygenase derivatives which also play a role in diabetic nephropathy. The present study was thus designed to examine the effect of an antioxidant and a lipoxygenase inhibitor, nordihydroguairetic acid (NDGA), on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) in rats. After the 4th week of STZ injection, NDGA (5 and 10 mg/kg) was given subcutaneously (s.c.) for another 4 weeks to both control and diabetic rats. At the end of the 8th week, diabetic rats exhibited renal dysfunction as evidenced by reduced creatinine and urea clearance along with enhanced albumin excretion rate as compared with control rats. Biochemical analysis of kidneys revealed a marked increase in oxidative stress demonstrated by increased lipid peroxidation and decreased activities of key antioxidant enzymes, glutathione (GSH), superoxide dismutase (SOD) and catalase in diabetic rats. Chronic treatment with NDGA in diabetic rats significantly prevented both renal dysfunction and oxidative stress as compared with vehicle-treated diabetic rats. The kidneys of diabetic rats showed morphological changes such as hyaline casts, glomerular thickening and moderate interstitial fibrosis and arteriolopathy, whereas NDGA administration in diabetic rats markedly prevented renal morphological alterations. These results emphasize the role of oxidative stress in the pathophysiology of diabetic nephropathy and point towards the potential of NDGA as a complementary therapy for the prevention/treatment of diabetic nephropathy.     

替米沙坦对2型糖尿病大鼠肾脏内氧化立激及NIH3T3细胞中促成熟因子活性的影响

目的探讨替米沙坦对2型糖尿病大鼠肾脏氧化应激和NIH3T3细胞中促成熟因子（MPF）活性的影响。方法将动物分为正常对照组、糖尿病组及替米沙坦治疗组，检测各组给药4，5，11，17周后的血糖、血胰岛素、血脂（TG，TC），11，17周的血肌酐（Scr）、血尿素氮（BUN）、尿微白蛋白排泄率（UAE）、肾组织中丙二醛（MDA）含量、铜，锌-超氧化物歧化酶（Cu，Zn—SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化酶（GSH—Px）及MPF活性。结果与糖尿病组相比，替米沙坦治疗组血糖、血胰岛素及血脂无明显变化，而Scr，BUN，UAE、肾脏MDA含量、肾细胞膜MPF均明显下降，肾脏抗氧化酶活性（Cu，Zn—SOD，CAT，GSH—Px）则明显上升。肾脏内MDA含量的变化及抗氧化酶活性的变化与细胞膜、细胞浆MPF活性的变化相关。结论替米沙坦可以抑制2型糖尿病大鼠肾脏内的氧化应激，并且可能与其下调NIH3T3细胞中MPF活性有关。     

Beneficial effect of shallot (Allium ascalonicum L.) extract on cyclosporine nephrotoxicity in rats.

The clinical use of an immunosuppressive cyclosporine A (CsA) is limited by its serious nephrotoxic effect. Evidences have suggested the role of oxidative stress in its pathogenesis. Shallot (Allium ascalonicum L.) has recently been shown to possess antioxidative and free radical scavenging abilities. The present study was undertaken to investigate the possible beneficial effect of shallot extract on renal injury caused by CsA. Male Wistar rats were treated orally with vehicle, CsA (25 mg/kg), shallot extract (1 g/kg), and CsA plus shallot extract for 21 days. Renal function, histopathology, tissue malondialdehyde (MDA) and glutathione (GSH) levels were evaluated 24 h after the last treatment. CsA-induced nephrotoxicity was evidenced by increased blood urea nitrogen and serum creatinine, but decreased urea and creatinine clearance. The kidney of CsA treated rats exhibited severe vacuolations and tubular necrosis. CsA also induced oxidative stress, as indicated by increased renal MDA and reduced GSH concentrations. Administration of shallot extract along with CsA counteracted the deleterious effects of CsA on renal dysfunction, oxidative stress markers, and morphological changes. These data indicate the protective potential of shallot extract against CsA nephrotoxicity and suggest a significant contribution of its antioxidant property to this beneficial effect.     

肾小球疾病116例临床与病理分析

目的：探讨肾小球疾病临床与病理特点。方法回顾性分析2010年1月～2013年6月在我院收治的成人肾小球疾病116例患者的临床病例资料,所有患者均经肾活检确诊为肾小球疾病,分析其肾脏病理类型,以及病理与临床表现的关系。结果116例成人肾小球疾病患者中84例患者为原发性肾小球疾病,占72.4%;32例患者为继发性肾小球疾病,占27.6%。其中IgA肾病是原发性肾小球肾炎的主要病理类型,占39.8%。对于肾病综合征、肾炎综合征的患者,不伴有肾小管间质损害的患者与伴有肾小管间质损害的患者相比,两组间尿白蛋白,血肌酐、血尿酸之间的差异具有统计学意义（P＜0.05）。结论肾小球疾病中以原发性肾小球肾炎最为常见,其中IgA肾病是原发性肾小球肾炎最常见的病理类型;而狼疮性肾炎是成人继发性肾小球肾炎最常见的病理类型。不同的肾小球疾病病理类型可有不同的临床表现,尿白蛋白、血肌酐、血尿酸在肾小球疾病的肾小管间质损害中起着一定作用。     

Protective effect of naringin, a bioflavonoid on glycerol-induced acute renal failure in rat kidney

Rhabdomyolysis-induced myoglobinuric acute renal failure accounts for about 10-40% of all cases of acute renal failure (ARF). Reactive oxygen intermediates have been demonstrated to play an etiological role in myoglobinuric renal failure. This study was designed to investigate the effect of naringin, a bioflavonoid with antioxidant potential, in glycerol-induced ARF in rats. Five groups of rats were employed in this study, group I served as control, group II was given 50% glycerol (8 ml/kg, intramuscularly), group III, IV, and V were given glycerol plus naringin 100, 200, and 400mg/kg p.o. route, respectively) 60 min prior to the glycerol injection. Renal injury was assessed by measuring plasma creatinine, blood urea nitrogen, creatinine, and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels, and by enzymatic activity of catalase, glutathione reductase, and superoxide dismutase. Glycerol treatment resulted in a marked renal oxidative stress and significantly deranged the renal functions. Pretreatment of animals with naringin 60 min prior to glycerol injection markedly attenuated renal dysfunction, morphological alterations, reduced elevated thiobarbituric acid reacting substances (TBARS), and restored the depleted renal antioxidant enzymes. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction, and suggest a protective effect of naringin in glycerol-induced renal failure in rats.     

Protective effect of herbomineral formulation (Dolabi) on early diabetic nephropathy in streptozotocin-induced diabetic rats

The effect of a herbomineral formulation (HMF) on early diabetic nephropathy was investigated. Diabetes was induced in Wistar rats by administering streptozotocin (55 mg/kg, intraperitoneally). The occurrence of early diabetic nephropathy in rats was revealed by high plasma glucose and depleted liver glycogen, decreased glucose uptake by peripheral tissue, impaired renal function, increased antioxidants and lipid peroxidation in kidney. These changes were accompanied by elevated malondialdehyde, glutathione and superoxide dismutase activity in kidney. Furthermore, increased total urine volume, urinary albumin excretion rate, urinary albumin to creatinine ratio, increased relative kidney weight, decreased glomerular filtration rate (GFR) and urinary creatinine were also observed in diabetic nephropathy rats. HMF treatment significantly lowered blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen, triglycerides, total cholesterol, serum albumin level, total urine volume, urinary albumin excretion rate, urinary albumin to creatinine ratio and relative kidney weight, and increased urinary creatinine and GFR. Altered levels of antioxidants, viz. lipid peroxidation, glutathione and superoxide dismutase (SOD), in kidney of diabetic nephropathy rats were restored. Histopathological findings indicated dense mesangial matrix in the glomeruli of diabetic nephropathy rats, which may be due to over-activation of matrix metalloproteinases and was reduced following HMF treatment. Our experimental findings clearly demonstrate that HMF has an ability to prevent the progression of early diabetic nephropathy. Such protective effect of HMF might be due to the presence of flavonoids (catechin, quercetin, rutin) and triterpene saponins (oleanolic acid and gymnemic acid) which are known to possess potent antioxidant properties.     

Effects of first and second generation antihistamines on muscarinic induced mucus gland cell ion transport

Background

In India, Curcumin (CMN) is popularly known as "Haldi", and has been well studied due to its economic importance. Traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism and sinusitis. This study was designed to examine the possible beneficial effect of CMN in preventing the acute renal failure and related oxidative stress caused by chronic administration of cyclosporine (CsA) in rats. CMN was administered concurrently with CsA (20 mg/kg/day s.c) for 21 days. Oxidative stress in kidney tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) content, superoxide dismutase (SOD), and Catalase (CAT). Nitrite levels were estimated in serum and tissue homogenates.

Results

CsA administration for 21 days produced elevated levels of TBARS and marked depletion of renal endogenous antioxidant enzymes and deteriorated the renal function as assessed by increased serum creatinine, Blood Urea Nitrogen (BUN) and decreased creatinine and urea clearance as compared to vehicle treated rats. CMN markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction increased the levels of antioxidant enzymes in CsA treated rats and normalized the altered renal morphology.

Conclusion

In conclusion our study showed that CMN through its antioxidant activity effectively salvaged CsA nephrotoxicity.     

Quercetin, an anti-oxidant bioflavonoid, attenuates diabetic nephropathy in rats

1. Diabetic nephropathy is an important microvascular complication and one of the main causes of end-stage renal disease. Many in vivo and in vitro studies have indicated that oxidative stress is one of the major pathophysiological mechanisms involved in the development of diabetic nephropathy. In the present study, we examined the effect of an anti-oxidant bioflavonoid quercetin on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. 2. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ (45 mg/kg). Four weeks after STZ injection, quercetin (10 mg/kg per day) was given orally for 4 weeks in both control and diabetic rats. Plasma glucose levels and bodyweights were measured at 4 and 8 weeks after the STZ injection. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The renal oxidative stress marker malonaldehyde, glutathione levels and the anti-oxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. 3. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in bodyweight compared with age-matched control rats. After 8 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Treatment with quercetin significantly attenuated renal dysfunction and oxidative stress in diabetic rats. 4. These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible anti-oxidative mechanism being responsible for the nephroprotective action of quercetin.     

Protective effect of Hachimi-jio-gan against renal failure in a subtotal nephrectomy rat model

The protective effect of Hachimi-jio-gan extract against chronic renal failure in a subtotal nephrectomy rat model was investigated. The level of serum urea nitrogen by nephrectomy was increased over 15 weeks, but the administration of Hachimi-jio-gan at 50 and 200 mg led to the decrease. In addition, the levels of creatinine (Cr), urinary methylguanidine (MG) and MG/Cr were increased, whereas Cr clearance dramatically decreased in nephrectomized rats. However, oral administration of Hachimi-jio-gan extract prevented the elevation of these uremic toxins in serum and urine, and the production of hydroxyl radical. Moreover, nephrectomy led to a significant decline in superoxide dismutase (SOD) and catalase activities, but increased glutathione peroxidase activity compared with normal levels, indicating an abnormal antioxidative system. The increased activity of both SOD and catalase by the oral administration of Hachimi-jio-gan suggested that these enzymes are associated with the protective role of Hachimi-jio-gan extract against oxidative stress by nephrectomy. Moreover, the decrease in serum albumin in nephrectomized control rats was increased and proteinuria was ameliorated by the administration of Hachimi-jio-gan with improved glomerular hyalinosis, interstitial fibrosis and inflammation, suggesting the beneficial effect of Hachimi-jio-gan to prevent glomerular sclerosis and progressive renal fibrosis. This study suggests that Hachimi-jio-gan plays a protective role in the progression of chronic renal failure through the decline in uremic toxins, elevation of antioxidative enzyme activity such as SOD and catalase, and amelioration of histopathological lesions in the kidney.     

Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats

The present study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced nephrotoxicity and oxidative stress in rats. We also investigated the effects of MT on induction of apoptotic cell death and its potential mechanisms in renal tissues in response to GM treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) MT (15?mg/kg/day), (3) GM (100?mg/kg/day), and (4) GM&MT. GM caused severe nephrotoxicity as evidenced by increased serum blood urea nitrogen and creatinine levels, increased renal tubular cell apoptosis, and increased Bcl2-associated X protein and cleaved caspase-3 protein expression. Additionally, GM treatment caused an increase in levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) protein expression in renal tissues. The significant decreases in glutathione content, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities and the increase in malondialdehyde content indicated that GM-induced tissue injury was mediated through oxidative reactions. In contrast, MT treatment protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by the GM treatment. Histopathological studies confirmed the renoprotective effect of MT. These results indicate that MT prevents nephrotoxicity induced by GM in rats, presumably because it is a potent antioxidant, restores antioxidant enzyme activity, and blocks NF-κB and iNOS activation in rat kidney.     

Protective role of dietary Spirulina platensis against diazinon-induced Oxidative damage in Nile tilapia; Oreochromis niloticus

The current study was performed to investigate the ameliorating effect of dietary supplementation of 0.5 and 1% Spiurolina platensis (SP) diet against the sub-acute toxicity of diazinon (DZN) 0.28 mg/L in Nile tilapia. At the end of experiment after 28 days, hepatic and renal damage markers (aspartate transaminase, alanine transaminase, alkaline phosphatase, urea, uric acid and creatinine), serum biochemical parameters (total proteins, albumin, cholesterol and glucose) and tissue antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and malondialdehyde) were detesrmined. The results of the current study revealed significant improvement in hepatic and renal damage markers after SP supplementation in fish exposed to DZN toxicity. Moreover, SP improved serum biochemical markers through increasing serum albumin and globulins with a significant decrease in serum glucose and cholesterol. In addition, liver, kidneys and gills antioxidant status showed a significant improvement after SP supplemented to fish exposed to DZN where a significant increase in tissue antioxidant activity were observed with a significant decline in lipid peroxidation levels. It can be concluded that, SP supplementation attenuated the toxic effect of DZN toxicity in Nile tilapia through improving liver and kidney functions with a significant enhancement of tissue antioxidant status.     

Dipyridamole attenuates ischemia reperfusion induced acute kidney injury through adenosinergic A1 and A2A receptor agonism in rats

Dipyridamole (DYP) is an anti-platelet agent with marked vasodilator, anti-oxidant, and anti-inflammatory activity. The present study investigated the role of adenosine receptors in DYP-mediated protection against ischemia reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h. The renal damage induced by ischemia reperfusion injury (IRI) was assessed by measuring creatinine clearance, blood urea nitrogen, uric acid, plasma potassium, fractional excretion of sodium, and microproteinuria in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The hematoxylin-eosin staining was carried out to observe histopathological changes in renal tissues. DYP (10 and 30 mg/kg, intraperitoneal, i.p.) was administered 30 min before subjecting the rats to renal IRI. In separate groups, caffeine (50 mg/kg, i.p.), an adenosinergic A1 and A2A receptor antagonist was administered with and without DYP treatment before subjecting the rats to renal IRI. The ischemia reperfusion-induced AKI was demonstrated by significant changes in serum as well as urinary parameters, enhanced oxidative stress, and histopathological changes in renal tissues. The administration of DYP demonstrated protection against AKI. The prior treatment with caffeine abolished DYP-mediated reno-protection suggesting role of A1 and A2A adenosine receptors in DYP-mediated reno-protection in rats. It is concluded that adenosine receptors find their definite involvement in DYP-mediated anti-oxidative and reno-protective effect against ischemia reperfusion-induced AKI.     

Protective effects of α-tocopherol against oxidative stress related to nephrotoxicity by monosodium glutamate in rats

Context: Chronic oral intake of high doses of monosodium glutamate (MSG) could be harmful to tissues and organs. Oxidative stress enhances membrane damage by lipid peroxidation and alterations of antioxidant enzymes, which affects the functional activity of organs. Antioxidant vitamins have the capacity to regulate the oxidative stress related functional and pathological processes. Objective: In this study, the protective role of α-tocopherol against MSG-induced nephrotoxicity was analyzed. Materials and methods: MSG (4?g/kg) was given orally to female wistar rats for a period of 180 days. Renal function parameters (urea, uric acid, and creatinine), lipid peroxidation markers (malondialdehyde and conjugated dienes), antioxidant system (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, and reduced glutathione), and histopathology were investigated. All tests were done in rats treated with MSG and at two different doses of α-tocopherol (100 and 200?mg/kg). Results: Oral exposure of MSG significantly increased renal function markers, lipid peroxidation byproducts, and altered antioxidant system. Moreover, the kidney showed congested glomeruli, tubular swelling, capillary congestion and microhemorrhages in stromal areas of the tubules. Co-administration of MSG and α-tocopherol (200?mg/kg) significantly reduced the oxidative damage compared with MSG-treated group and also restored the normal renal function. Discussion: The results indicated that oxidative stress was involved in MSG-induced functional and pathological changes in the kidney. α-tocopherol modulates the functional disorder and maintains the normal architecture of renal tissue by reducing oxidative stress. Conclusion: The α-tocopherol may be a potent protective agent in combating MSG-induced renal toxicity.     

Catechin, a natural antioxidant protects against rhabdomyolysis-induced myoglobinuric acute renal failure.

Rhabdomyolysis-induced myoglobinuric acute renal failure accounts for about 10-40% of all cases of acute renal failure (ARF). Reactive oxygen intermediates have been demonstrated to play an etiological role in myoglobinuric renal failure. This study was performed to explore the protective effect of catechin-a natural antioxidant in an experimental model of myoglobinuric ARF in rats. Four groups of rats were employed in this study, group 1 served as control, group 2 was given 50% glycerol (8 ml kg(-1), i.m.), group 3, glycerol plus catechin (40 mg kg(-1), p.o. for 4 days, twice a day) and group 4 was given only catechin (40 mg kg(-1), p.o.), respectively. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), creatinine, and urea clearance. The oxidative stress was measured by renal malondialdehyde (MDA) levels, reduced glutathione levels and by enzymatic activity of catalase, glutathione reductase (GR) and superoxide dismutase (SOD). Glycerol administration resulted in a marked renal oxidative stress, significantly deranged the renal functions as well as renal morphology. All these factors were significantly improved by catechin treatment. Catechin, due to its antioxidative activity, reduced the toxicity of myoglobin in the renal tissues, and thus exerted a renoprotective effect in this rhabdomyolysis mimicking model.     

Dose-response studies of gentamicin nephrotoxicity in rats with experimental renal dysfunction. II. Polyvinyl alcohol glomerulopathy

Animal studies involving concurrent pathophysiologic states, including experimental renal dysfunction, are useful for a proper understanding of the mechanisms of gentamicin nephrotoxicity and acute renal failure. This study examined gentamicin nephrotoxicity in a model of glomerular dysfunction in rats. Administration of medium molecular weight polyvinyl alcohol (PVA) produced a glomerulopathy, with characteristic accumulation of macromolecular PVA in the glomerular mesangium without altering glomerular filtration or causing proteinuria. Subsequent daily doses of gentamicin ranging from 0 to 120 mg/kg elicited a dose-response nephrotoxicity in both control and PVA-pretreated rats after 6 or 12 days of drug. Based on statistical analysis of renal clearances of creatinine, urea, sodium, and potassium; serum creatinine and urea nitrogen; urinary N-acetyl-beta-D-glucosaminidase excretion (6 days only); in vitro renal cortical transport of tetraethylammonium (TEA) (6 days); and quantified light-microscopic data (12 days), PVA induced an early (6 days) sensitivity to gentamicin nephrotoxicity. By 12 days, there were no differences in the responses of control and PVA rats to gentamicin. Single-dose gentamicin clearance, volume of distribution, and half-life were not altered by PVA and renal concentrations at 6 days were generally lower in these rats. Results of TEA transport studies tend to rule out PVA-induced metabolic lesions in the proximal tubular epithelium as the mechanism for the early sensitivity. This investigation demonstrates altered gentamicin nephrotoxicity in rats with an otherwise benign glomerulopathy and, combined with similar conclusions from a related study in subtotally nephrectomized rats, presents further evidence that the underlying pathophysiologic state of the kidney is an important factor in the renal response to nephrotoxins.     

保肾降糖胶囊对糖尿病大鼠降糖及肾保护作用研究

目的：探讨保肾降糖胶囊对糖尿病大鼠肾脏的保护作用及其机制。方法：将SD大鼠分为6组,测定第1、8周血清肌酐及血清胰岛素、胰高血糖素、糖化血红蛋白等生化指标和尿液各项指标;取肾上腺皮质测定SOD、GSH-Px、MDA、NO2-/NO3-和NOS,评价保肾降糖胶囊的降糖作用及对糖尿病肾病的保护作用。结果：给药保肾降糖胶囊60d后,高剂量组和中剂量组大鼠的血糖值明显降低,血清肌酐清除率显著增加,尿微量清蛋白排泄率明显降低,血清胰岛素明显升高,胰高血糖素、糖化血红蛋白、尿微量清蛋白均显著降低;肾上腺皮质中的T-SOD、GSH-Px、NO^2-/NO^3-、NOS含量增加,MDA含量显著降低。结论：保肾降糖胶囊可降低糖尿病大鼠的血糖,明显减轻糖尿病大鼠蛋白尿,改善肾小球滤过率。通过提高抗氧化酶活性、清除ROS、增加NOS活性从而延缓肾小球硬化进程,减轻糖尿病肾病并发症。     

Beneficial effects of nilotinib,tyrosine kinase inhibitor on cyclosporine-A induced renal damage in rats

Nilotinib is a known tyrosine kinase inhibitor that has been approved for treatment of leukemia. The possible protective effect of nilotinib on cyclosporine A-induced nephropathy was investigated in this study and the possible underlying mechanism was explored. Nilotinib (25 mg/kg, orally) and cyclosporine A (15 mg/kg/day, subcutaneous) were given to male SD rats for 28 days. Cyclosporine A alone was found to significantly increase serum creatinine, blood urea nitrogen, lactate dehydrogenase, urinary micrototal protein, renal thiobarbituric acid reactive substance, Bax, cytosol cytochrome c release and nuclear factor kappa B activation. Moreover, cyclosporine A significantly reduced serum albumin, creatinine clearance, urinary total antioxidant, superoxide dismutase, glutathione and Bcl2 protein levels. Pathological results showed that in the model group; there was an obvious shrinkage and congestion of the glomeruli and widening of urinary spaces of renal corpuscles, in addition to marked renal tubular injury and fibrosis, while in the group pretreated with nilotinib all measured serum, renal and pathological changes were significantly reduced. This protective effect of nilotinib is linked to the enhanced antioxidant status and reduced inflammation and apoptosis induced by cyclosporine A.     

Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on absolute ethanol-induced injury in various organs of rats

In this study, the effect of combination of vitamin C (ascorbic acid), vitamin E (alpha -tocopherol), and selenium (sodium selenate) on ethanol-induced liver and intestine injury in rats was investigated. The ethanol-induced injury was produced by the administration of 1 ml of absolute ethanol to each rats. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and sodium selenate (Se) (0.5 mg/kg) for 3 days; 1 h after the final antioxidant administration, they were sacrificed. Lipid peroxidation and glutathione levels, catalase (CAT), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GP(x)) activities were determined in liver and intestine tissues. Myeloperoxidase (MPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) were determined in liver tissue. Also, CAT activity, urea, creatinine, uric acid, and total lipid levels were determined in serum samples. In the ethanol group, serum urea, creatinine, uric acid, and total lipid levels; liver and intestine LDH; liver MPO, AST, ALP, ALT, and GGT activities; and liver and intestine LPO levels increased, whereas serum CAT activity, liver and intestine GSH levels, and CAT, SOD, and GP(x) activities decreased. On the other hand, treatment with vitamin C, vitamin E, and Se reversed these effects. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced changes in lipid peroxidation, glutathione levels, and antioxidant enzyme activities in liver and intestine tissues, and in some serum parameters of rats.     

Role of GABAergic activity of sodium valproate against ischemia–reperfusion-induced acute kidney injury in rats

Gamma amino butyric acid (GABA) has been reported to be renoprotective in various preclinical studies. Sodium valproate (SVP) is documented to protect against renal injury through its histone deacetylase-inhibiting activity. The present study investigated the involvement of GABA_A receptors and the role of GABAergic activity of SVP against ischemia–reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The creatinine clearance, serum urea, uric acid, lactate dehydrogenase, potassium, fractional excretion of sodium, and microproteinuria were measured to assess kidney injury. The thiobarbituric acid-reactive substances, reduced glutathione level, myeloperoxidase, and catalase activity were assayed to assess oxidative stress in renal tissues along with hematoxylin–eosin staining to observe histopathological changes. The ischemia–reperfusion-induced AKI witnessed an increase in serum parameters, microproteinuria, oxidative stress, and histopathological changes in renal tissues. Picrotoxin aggravated ischemia–reperfusion injury-induced AKI confirming the role of GABA_A receptors in AKI. The SVP treatment afforded protection against AKI that was blocked by concurrent treatment with picrotoxin. Hence, it is concluded that regulation of GABA_A receptors is important for management of AKI. Moreover, the GABAergic activity of SVP is important for its renoprotective effect.