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.     

Effect of chronic treatment with losartan on streptozotocin-induced renal dysfunction

The present investigation was undertaken to study the effect of chronic treatment with angiotensin (AT₁) receptor antagonist losartan (2 mg/kg, p.o., 6 weeks) on streptozotocin (STZ) induced (45 mg/kg, i.v., single dose) renal dysfunctions in diabetic rats. Injection of streptozotocin produced not only the cardinal symptoms of diabetes mellitus like loss of body weight, hyperglycemia, and hypoinsulinemia but also the renal dysfunctions. Losartan treatment significantly prevented all these changes except STZ-induced hypoinsulinemia. There was a significant elevation of blood pressure in diabetic rats and treatment with losartan significantly brought it back to normal. Renal dysfunction in diabetic rats was characterized by a significant decrease in creatinine clearance, elevated levels of electrolytes and renal hypertrophy. Treatment with losartan prevented these changes. A good correlation was found between biochemical parameters and histopathological abnormalities. Our data suggests that, losartan may be considered as the drug of choice when there is a co-existence of diabetes mellitus and hypertension with compromised kidney function.     

Effect of sarpogrelate on altered STZ-diabetes induced cardiovascular responses to 5-hydroxytryptamine in rats

Sarpogrelate, a specific 5-HT_2A receptor antagonist is reported to produce a number of beneficial cardiovascular effects in diabetes mellitus. In the present investigation we have studied the effects of sarpogrelate on 5-HT receptors in heart and platelets in streptozotocin (STZ)-diabetic rats. Diabetes was induced by a single tail vein injection of STZ (45 mg/kg) and sarpogrelate (1 mg/kg, i.p.) was administered daily for 6 weeks. Injection of STZ produced significant loss of body weight, polyphagia, polydypsia, hyperglycemia, hypoinsulinemia, hypertension and bradycardia. Treatment with sarpogrelate significantly lowered fasting glucose levels with corresponding increase in insulin levels. It also significantly prevented STZ-induced polydypsia, hyperphagia, hypertension, and bradycardia but not the loss of body weight. 5-HT produced dose-dependent positive inotropic effect that was found to be decreased significantly in STZ-diabetic rats. Hearts obtained from sarpogrelate treated diabetic rats did not show any decrease in responsiveness to 5-HT. Relative platelet aggregation per se was found to be higher in STZ-diabetic rats as compared to control and this was significantly prevented by sarpogrelate treatment. 5-HT produced a dose-dependent increase in platelet aggregation in non-diabetic and sarpogrelate treated diabetic rats. However, 5-HT failed to produce any increase in platelet aggregation in untreated diabetic rats. Our data suggest that STZ-induced diabetes may produce down-regulation of cardiac 5-HT_2A receptors and increased platelet aggregation. Treatment with sarpogrelate seems to prevent STZ-induced down-regulation of 5-HT receptors and increase in platelet activity in diabetic rats.     

STZ诱发实验恒河猴糖尿病性视网膜并发症模型的建立

目的　建立糖尿病性视网膜并发症 (DiabeticRetinopathy ,DR)动物模型。方法　本研究选用 4只健康成熟的雄性恒河猴分别以剂量为 6 0mg kg、4 5mg kg静脉一次注射及 30mg kg静脉二次注射 (中间间隔 15d)链脲佐菌素 (Streptozotocin ,STZ)。结果　使用不同剂量的STZ注射恒河猴 ,分别造成了胰岛素依赖性糖尿病 (InsulinDepen dentDiabetesMellitus ,IDDM)及慢性持续性高血糖症 (StateofChronicHyperglycemia,SCH)两种类型的模型 ,从而诱导出不同程度的DR。眼底荧光造影结果显示∶用药后 6 3～ 91d4只实验猴均出现不同程度的视网膜病 ,分别显示早期眼底微血管动脉扩张 ,视网膜出血瘤 ,微血管瘤及新生血管、晚期白内障等。结论　本研究所建立的糖尿病性视网膜并发症模型 ,对于进一步研究糖尿病及其并发症的发病机理 ,筛选及开发治疗糖尿病性视网膜病的新药及药物安全性评价将会具有广阔的应用前景     

链脲佐菌素诱导SD和Wistar大鼠糖尿病模型的影响因素

目的通过注射链脲佐菌素（STZ）制作SD和Wistar大鼠糖尿病模型,观察大鼠品系、给药剂量、给药次数对大鼠成模率、死亡率的影响,同时研究利用口服葡萄糖耐量试验（OGTT）判断大鼠糖尿病成模率的意义。方法设置共同的正常对照组,①Wistar大鼠随机分为中剂量组（55 mg/kg）和高剂量组（65 mg/kg）;②SD大鼠一次性腹腔注射STZ（55 mg/kg）,与①中的Wistar大鼠作对比;③SD大鼠随机分为一次给药组和两次给药组,注射剂量均为55 mg/kg,观察期间进行OGTT。结果①Wistar大鼠成模率和死亡率均高于SD大鼠;②采用SD大鼠、中剂量给药和两次给药的方式可提高成模率,并降低死亡率;③在有明确胰岛病理改变的模型组大鼠,其OGTT异常阳性率显著高于空腹血糖异常阳性率。结论用STZ诱导糖尿病模型是一种稳定可靠的方法。Wistar大鼠成模率和死亡率均高于SD大鼠;选用中剂量给药及两次给药的方式可提高SD大鼠成模率,并降低死亡率,维持时间较长。在动物实验中OGTT比空腹血糖监测更有诊断意义,不易造成漏诊。     

Protective effect of cicletanine on renal function in diabetic spontaneously hypertensive rats.

Hypertension and diabetes are commonly associated and strongly predispose to renal injuries. In general, antihypertensive therapies protect from these damages, but the effect of cicletanine, a new type of antihypertensive drug, is unknown. This study examines the effects of cicletanine on renal failure in spontaneously hypertensive rats with diabetes (SHRD). Diabetes mellitus was induced with streptozotocin in uninephrectomized SHR. Rats received the vehicle, 10 mg or 50 mg/kg per day of cicletanine for 6 weeks. Age-matched untreated Wistar-Kyoto rats were used as controls. Systolic blood pressure (SBP), microalbuminuria and proteinuria were assessed throughout the treatment. At the end of the study, creatinine clearance measurements and histological analysis of kidneys were performed. Cicletanine did not affect SBP but decreased the elevated albuminuria of diabetic SHR in a dose-dependent manner. Similar results were obtained for proteinuria. Treatment with the high dose of cicletanine also normalized the altered creatinine clearance of diabetic SHR. These results indicate that cicletanine has a renal-protective action, probably blood pressure-independent, in a model combining hypertension and diabetes. The mechanism of renal-protection of cicletanine is not clearly established but may be due to the stimulation of arterial prostacyclin synthesis and/or to the reduction of intraglomerular capillary pressure.     

延长糖尿病模型大鼠生存期对糖尿病视网膜病变的影响

目的延长糖尿病模型大鼠生存期,动态观察糖尿病视网膜病变(DR)的形成和发展过程。方法雄性SD大鼠70只,随机分成对照组(20只)和模型组(50只),采用链脲佐菌素(STZ)60 mg/(kg.bw)体重腹腔1次注射造模,分别于69、、12月时处死取眼球,采用视网膜微血管消化铺片技术观察糖尿病视网膜病变的微血管形态学改变。结果糖尿病大鼠DR样病变随着病程的延长病变呈多样性改变,以12月DR出现的小动脉硬化尤为严重。结论糖尿病大鼠生存期的延长对糖尿病视网膜病变的研究有着积极的意义。     

Parameters of systemic hemodynamics in conscious rats with acute streptozotocin diabetes]

The effect of acute streptozotocin-induced diabetes mellitus on the systemic hemodynamic parameters was studied in conscious rats by thermodilution technique. Male Wistar rats were made diabetic with a single intravenous injection of streptozotocin (STZ, 50 mg/kg). The most important finding of this work was the elucidation of the systemic vasodilation and increased cardiac index one day after STZ injection. Such alteration in hemodynamic parameters could result in the increased blood flow and capillary hypertension in some vascular beds and, therefore, be considered as a pathogenic factor in the development of diabetic microangiopathy.     

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.     

Angiotensin II and endothelin-1 augment the vascular complications of diabetes via JAK2 activation

The JAK/STAT pathway is activated in vitro by angiotensin II (ANG II) and endothelin-1 (ET-1), which are implicated in the development of diabetic complications. We hypothesized that ANG II and ET-1 activate the JAK/STAT pathway in vivo to participate in the development of diabetic vascular complications. Using male Sprague-Dawley rats, we performed a time course study [days 7, 14, and 28 after streptozotocin (STZ) injection] to determine changes in phosphorylation of JAK2, STAT1, and STAT3 in thoracic aorta using standard Western blot techniques. On day 7 there was no change in phosphorylation of JAK2, STAT1, and STAT3. Phosphorylation of JAK2, STAT1, and STAT3 was significantly increased on days 14 and 28 and was inhibited by treatment with candesartan (AT(1) receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), atrasentan (ET(A) receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), and AG-490 (JAK2 inhibitor, 5 mg x kg(-1) x day(-1) intraperitoneally). On day 28, treatment with all inhibitors prevented the significant increase in systolic blood pressure (SBP; tail cuff) of STZ-induced diabetic rats (SBP: 157 +/- 9.0, 130 +/- 3.3, 128 +/- 6.8, and 131 +/- 10.4 mmHg in STZ, STZ-candesartan, STZ-atrasentan, and STZ-AG-490 rats, respectively). In isolated tissue bath studies, diabetic rats displayed impaired endothelium-dependent relaxation in aorta (maximal relaxation: 95.3 +/- 3.0, 92.6 +/- 7.4, 76.9 +/- 12.1, and 38.3 +/- 13.1% in sham, sham + AG-490, STZ + AG-490, and STZ rats, respectively). Treatment of rats with AG-490 restored endothelium-dependent relaxation in aorta from diabetic rats at 14 and 28 days of treatment. These results demonstrate that JAK2 activation in vivo participates in the development of vascular complications associated with STZ-induced diabetes.     

Glabridin as a major active isoflavan from Glycyrrhiza glabra (licorice) reverses learning and memory deficits in diabetic rats

Cognitive impairment occurs in diabetes mellitus. Glabridin as a major active flavonoids in Glycyrrhiza glabra (licorice) improves learning and memory in mice. In the present study, we investigated the effect of chronic treatment with glabridin (5, 25 and 50 mg/kg, p.o.) on cognitive function in control and streptozotocin (STZ)-induced diabetic rats.Animals were divided into untreated control, glabridin-treated control (5, 25 and 50 mg/kg), untreated diabetic and glabridin treated diabetic (5, 25 and 50 mg/kg) groups. Treatments were begun at the onset of hyperglycemia. Passive avoidance learning (PAL) and memory was assessed 30 days later. Diabetes caused cognition deficits in the PAL and memory paradigm. While oral glabridin administration (25 and 50 mg/kg) improved learning and memory in non-diabetic rats, it reversed learning and memory deficits of diabetic rats. Low dose glabridin (5 mg/kg) did not alter cognitive function in non-diabetic and diabetic groups. Glabridin treatment partially improved the reduced body weight and hyperglycemia of diabetic rats although the differences were not significant. The combination of antioxidant, neuroprotective and anticholinesterase properties of glabridin may all be responsible for the observed effects. These results show that glabridin prevented the deleterious effects of diabetes on learning and memory in rats. Further studies are warranted for clinical use of glabridin in the management of demented diabetic patients.     

The effects of streptozotocin induced diabetes mellitus and fish oil compound on gene expression of atrial natriuretic peptide in rat.

1. Adult male Wistar rats were injected with streptozotocin (STZ: 55 mg/kg) for inducing diabetes. Then blood and atria for RNA extraction were withdrawn from rats treated 3 and 11 weeks previously with STZ respectively. Atrial total RNA were extracted with cold phenol method. The ANP mRNA contents were determined using Dot blot hybridization technique with alpha-32-P-labelled r-prepro ANP cDNA probe. 2. Plasma glucose was increased and plasma immunoreactive insulin was lowered in rats at 3 and 11 weeks after injection of STZ. ANP gene expression in diabetic rats was depressed. ANP mRNA contents in rats treated 3 and 11 weeks with STZ were 86.4% and 31.7% of that of control rats. 3. Three weeks after treatment of STZ, the rats were gastrically perfused with FOC (Fish Oil Compound) (0.355 ml/kg) once a day successively until 11 weeks. This treatment induces lower blood pressure in rats. ANP gene expression in FOC group was apparently recovered which had been decreased because of the effect of diabetes mellitus.     

Effect of hypertension on the development of diabetic cardiomyopathy

The effect of hypertension on the progression of diabetic cardiomyopathy was examined by attempting to induce a similar level of diabetes in both spontaneously hypertensive rats (SHR) and Wistar rats. Streptozotocin (STZ) was injected into SHR (45 mg/kg) and Wistar rats (55 mg/kg) before (eight weeks of age) and after (twelve weeks of age) the development of hypertension in the SHR. For both groups of animals, induction of diabetes resulted in depressed weight gain, increased food and fluid consumption, hypoinsulinemia, hyperglycemia, and hypertriglyceridemia. For the rats injected at eight weeks of age, an oral glucose tolerance test (OGTT) demonstrated that although the SHR were significantly less diabetic than Wistar rats, the degree of cardiac dysfunction was equivalent in both strains. These results suggest that hypertension was interacting with the diabetic condition to impair cardiac performance. Injecting SHR at twelve weeks of age increased the severity of diabetes but interestingly did not depress heart function compared with the non-diabetic SHR group. Injecting Wistar rats at this age also increased the severity of diabetes, but unlike the SHR diabetic animals, these rats still had impaired cardiac performance. These results suggest that hypertension exacerbates the cardiac dysfunction seen during diabetes, especially when SHR rats are injected with STZ prior to the elevation of blood pressure. Moreover, in the SHR, the development of LV hypertrophy at the time of STZ injection may have compensated for the damaging effects of diabetes on the myocardium, thereby enabling the heart to perform normally.     

Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension

INTRODUCTIONThe streptozotocin [STZ]-induced diabetes and NO-deficient hypertension are widely used experimental modelsfor the investigation of heart failure [1-4]. Cardiac dys-function in both models is consequence of different sig-nal and metabolic dera…     

Euterpe oleracea Mart. (açaí) seed extract associated with exercise training reduces hepatic steatosis in type 2 diabetic male rats

Type 2 diabetes mellitus contributes to an increased risk of metabolic and morphological changes in key organs, such as the liver. We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on hepatic steatosis induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks, followed by a single low dose of STZ (35 mg/kg i.p.). Control and diabetic groups were subdivided into four groups that were fed with standard chow diet for 4 weeks. Control (C) group was subdivided into Sedentary C, Training C, ASE Sedentary C and ASE Training C. Diabetic (D) group was subdivided into Sedentary D, Training D, ASE Sedentary D and ASE Training D. ASE (200 mg/kg/day) was administered by intragastric gavage, and the exercise training was performed on a treadmill (30 min/day; 5 days/week). Treatment with ASE associated with exercise training reduced the blood glucose (70.2%), total cholesterol (81.2%), aspartate aminotransferase (51.7%) and hepatic triglyceride levels (66.8%) and steatosis (72%) in ASE Training D group compared with the Sedentary D group. ASE associated with exercise training reduced the hepatic lipogenic proteins’ expression (77.3%) and increased the antioxidant defense (63.1%), pAMPK expression (70.2%), cholesterol transporters (71.1%) and the pLKB1/LKB1 ratio (57.1%) in type 2 diabetic rats. In conclusion, ASE treatment associated with exercise training protects against hepatic steatosis in diabetic rats by reducing hepatic lipogenesis and increasing antioxidant defense and cholesterol excretion.     

Puerarin decreases apoptosis of retinal pigment epithelial cells in diabetic rats by reducing peroxynitrite level and iNOS expression

The purpose of this study was to investigate the protective effect of puerarin on retina pigment epithelial (RPE) cells of diabetic rats against apoptosis. One hundred and eight Sprague-Dawley (SD) rats were randomly divided into 3 groups: control group, streptozotocin (STZ) group and puerarin group. STZ and puerarin groups received 3 d of STZ injection (45 mg/kg per day, i.p.). Additionally, puerarin groups were treated with puerarin (140 mg/kg, i.p.) from the 4th day to the end of experiment. The rats from different groups were sacrificed on 20, 40 and 60 d after STZ injection for harvesting RPE cells. Western blot analysis, DNA laddering, RT-PCR and immunohistochemistry were used for determining the expression of nitrotyrosine (NT, the foot print of peroxynitrite), cell apoptosis, iNOS mRNA and Fas/Fas ligand (FasL) signal transduction in RPE cells, respectively. The results showed that control group maintained low apoptosis level and little NT, iNOS mRNA, Fas/FasL protein expressions, as well as normal blood glucose and body weight during 60 d of the experiment. Compared with control group, STZ group showed obvious apoptosis and higher NT, iNOS mRNA, Fas/FasL protein expressions from 20 d after STZ injection. Puerarin relieved apoptosis of RPE cells and decreased NT, iNOS mRNA, Fas/FasL protein expressions in puerarin group 20 or 40 d after STZ injection, compared with STZ group. These results suggest puerarin can decrease RPE cells apoptosis in diabetic rats by reducing peroxynitrite level and iNOS expression, thus being a potential therapeutic agent in controlling of diabetic retinopathy.     

Effect of telmisartan on cardiovascular complications associated with streptozotocin diabetic rats

Angiotensin receptor blockers provide cardiovascular protection in heart failure patients. We have studied the effect of 8 weeks treatment with telmisartan (5 mg kg(-1) day(-1)) on cardiovascular complications associated with streptozotocin (STZ) diabetic rats. Wistar rats were made diabetic with STZ (45 mg kg(-1), iv). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, reduction in heart rate and cardiac hypertrophy. Chronic treatment with telmisartan significantly (P < 0.05) prevented STZ induced hypertension and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly (P < 0.05) reduced the elevated cholesterol, very low density lipoprotein (VLDL) and triglyceride levels in diabetic rats and increased the lower high density lipoprotein (HDL)-cholesterol levels. Further, telmisartan produced a significant (P < 0.05) reduction in the elevated creatinine levels, CRP and levels of other cardiac enzyme markers like Lactate de-hydrogenase and creatinine kinase of diabetic rats. STZ-induced bradycardia was also prevented by telmisartan treatment and it also produced beneficial effect by preventing cardiac hypertrophy as evident from left ventricular collagen levels, cardiac hypertrophy index and left ventricular hypertrophy index of diabetic rats. Our data suggest that telmisartan prevents not only the STZ-induced metabolic abnormalities, but also cardiovascular complications.     

The influence of mildronate on peripheral neuropathy and some characteristics of glucose and lipid metabolism in rats with the streptozotocin model of diabetes mellitus

Rats with the streptozotocin (STZ) model of diabetes mellitus were treated with mildronate (100 mg/kg daily, per os or intraperitoneally) for 6 weeks. Body weight, blood glucose, triglycerides, ketone body concentrations, percent of glycated hemoglobin (HbA1c%), glucose tolerance, and the development of neuropathic pain were monitored throughout the whole experiment. The mildronate treatment completely prevented the development of the diabetic neuropathy from the first week up to the end of experiment. In the group of diabetic animals treated with mildronate a significant decrease of blood glucose was observed on the fourth week of the treatment, the level of triglycerides decreased from the third to sixth weeks. Mildronate also decreased accumulation of glycated hemoglobin on the sixth week and improved glucose tolerance compared with untreated animals. The data obtained confirm applicability of mildronate for therapy of diabetes mellitus and its complications.     

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     

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.