Superoxide dismutase, catalase and glutathione peroxidase in the spontaneously hypertensive rat kidney: effect of antioxidant-rich diet

BACKGROUND AND OBJECTIVE: Earlier studies have shown increased production of reactive oxygen species (ROS) and upregulation of ROS-generating enzyme, nicotinamide adenine dinucleotide (phosphate) oxidase, in the kidney of spontaneously hypertensive rats (SHR). This study aimed to examine the activities and protein abundance of the main antioxidant enzymes [i.e. superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)] in the kidney of SHR fed a regular or an antioxidant-rich diet. METHODS: Pregnant SHR and their offspring were fed either a regular diet or an antioxidant-rich diet (alpha-tocopherol, ascorbic acid, zinc and selenium) and observed for 6 months. Wistar-Kyoto (WKY) rats fed a regular or antioxidant-fortified diet served as controls. RESULTS: The untreated SHR showed severe hypertension and significant increases in plasma hydrogen peroxide and renal tissue nitrotyrosine abundance, indicating the presence of oxidative/nitrosative stress. Despite oxidative stress, Cu Zn SOD, CAT and GPX activities were unchanged in the cortex and medulla of untreated SHR. Immunodetectable Mn SOD was reduced in the medulla and elevated in the cortex, whereas, Cu Zn SOD protein was unchanged in the cortex and reduced in the medulla. By contrast, CAT protein abundance was increased in both cortex and medulla while GPX protein was elevated in the cortex and unchanged in the medulla. Comparison of protein abundance and activities of the antioxidant enzymes revealed significant discordance in the untreated SHR. Lifelong antioxidant therapy diminished the severity of hypertension, improved oxidative stress and ameliorated or reversed abnormalities of antioxidant enzyme expressions and activities. By contrast, antioxidant therapy had no effect on the measured parameters in the WKY rat controls. CONCLUSIONS: Oxidative stress in SHR was associated with a lack of coordinate upregulation of the antioxidant enzymes and discordance between their protein abundance and enzymatic activity. These findings suggest an impaired antioxidant defense system and the presence of functionally abnormal enzymes in the SHR kidney. Lifelong antioxidant therapy improved expression, activity and activity-to-mass relationship of the measured enzymes. The latter suggests oxidative and nitrosative modification of these molecules in the SHR kidney.     

Antioxidant therapy potentiates antihypertensive action of insulin in diabetic rats

BACKGROUND: Poorly controlled longstanding diabetes frequently results in sustained hypertension (HTN) which plays a major role in the pathogenesis of diabetic nephropathy. In addition, hyperglycemia, per se, causes a reversible rise in blood pressure (BP) and increases production of reactive oxygen species (ROS). Increased ROS activity may raise BP by promoting inactivation of nitric oxide (NO) and/or nonenzymatic generation of vasoconstrictive prostaglandins from peroxidation of arachidonic acid. Therefore, we hypothesized that antioxidant therapy may enhance the BP-lowering effect of glycemia control with insulin replacement in diabetes. METHODS: Male Sprague-Dawley rats were rendered diabetic by streptozotocin administration and randomized to untreated, antioxidant-treated (vitamin E-fortified food, tocopherol 5000 U/kg chow and vitamin C-fortified H2O, 1000 mg/L), insulin-treated and insulin plus antioxidant-treated groups. Normal rats fed a regular diet or antioxidant-fortified diet served as controls and monitored for 4 weeks. RESULTS: The diabetic animals showed marked hyperglycemia, HTN, proteinuria, depressed tissue glutathione level and elevated plasma lipid peroxidation product, malondialdehyde (MDA) denoting increased ROS activity. Insulin therapy alone resulted in significant, but incomplete reduction in BP and plasma MDA but not proteinuria. Antioxidant therapy alone had no effect on the measured parameters in either the diabetic or control animals. However, combined insulin and antioxidant therapies normalized BP, plasma MDA and urinary protein in the diabetic animals. As expected, uncontrolled diabetes resulted in glomerular hyperfiltration which was partially reversed by insulin therapy, but was unaffected by antioxidant therapy. CONCLUSION: Uncontrolled hyperglycemia in the early phase of diabetes was associated with elevated plasma MDA, HTN and proteinuria. Insulin therapy alone resulted in significant but incomplete reduction of plasma MDA and BP. Antioxidant therapy which was ineffective when given alone, normalized plasma MDA, BP and reduced urinary protein excretion when combined with insulin treatment.     

ANTIOXIDANT THERAPY POTENTIATES ANTIHYPERTENSIVE ACTION OF INSULIN IN DIABETIC RATS

Background: Poorly controlled longstanding diabetes frequently results in sustained hypertension (HTN) which plays a major role in the pathogenesis of diabetic nephropathy. In addition, hyperglycemia, per se, causes a reversible rise in blood pressure (BP) and increases production of reactive oxygen species (ROS). Increased ROS activity may raise BP by promoting inactivation of nitric oxide (NO) and/or nonenzymatic generation of vasoconstrictive prostaglandins from peroxidation of arachidonic acid. Therefore, we hypothesized that antioxidant therapy may enhance the BP-lowering effect of glycemia control with insulin replacement in diabetes. Methods: Male Sprague-Dawley rats were rendered diabetic by streptozotocin administration and randomized to untreated, antioxidant-treated (vitamin E-fortified food, tocopherol 5000?U/kg chow and vitamin C-fortified H₂O, 1000?mg/L), insulin-treated and insulin plus antioxidant-treated groups. Normal rats fed a regular diet or antioxidant-fortified diet served as controls and monitored for 4 weeks. Results: The diabetic animals showed marked hyperglycemia, HTN, proteinuria, depressed tissue glutathione level and elevated plasma lipid peroxidation product, malondialdehyde (MDA) denoting increased ROS activity. Insulin therapy alone resulted in significant, but incomplete reduction in BP and plasma MDA but not proteinuria. Antioxidant therapy alone had no effect on the measured parameters in either the diabetic or control animals. However, combined insulin and antioxidant therapies normalized BP, plasma MDA and urinary protein in the diabetic animals. As expected, uncontrolled diabetes resulted in glomerular hyperfiltration which was partially reversed by insulin therapy, but was unaffected by antioxidant therapy. Conclusion: Uncontrolled hyperglycemia in the early phase of diabetes was associated with elevated plasma MDA, HTN and proteinuria. Insulin therapy alone resulted in significant but incomplete reduction of plasma MDA and BP. Antioxidant therapy which was ineffective when given alone, normalized plasma MDA, BP and reduced urinary protein excretion when combined with insulin treatment.     

Carvedilol improved diabetic rat cardiac function depending on antioxidant ability

The risk for cardiovascular disease is significantly high in diabetes mellitus. Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has a close connection with antagonizing oxidative stress destroy in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant and free radical scavenger properties. To study the effect of carvedilol on the antioxidant status and expression of Bcl-2 in healthy and diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage (1 or 10mg/kg/d) carvedilol-administrated for 5 weeks, hemodynamic parameters, the levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and expression of Bcl-2 mRNA in the cardiac tissues of all six groups were measured. Diabetic rats had higher left ventricular end diastolic pressure (LVEDP), lower maximal rate of rise/fall left ventricle pressure development and decline (+/-dP/dtmax). These parameters were improved by administration of carvedilol. Diabetic rats showed elevated MDA level and CAT activity, but lower activities of SOD and GSH-Px. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicate that carvedilol improves cardiac function via its antioxidant property in diabetic rats partly.     

Maternal-foetal status of copper,iron, molybdenum,selenium and zinc in obese gestational diabetic pregnancies

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Paucity of data on maternal-foetal status of essential trace elements in obese diabetic pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous blood samples were collected from obese gestational diabetic patients (Body Mass Index (BMI) >30) and control obese pregnant women (BMI>30) at time of spontaneous delivery or caesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se and Zn were determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant (TAO) in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-foetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se and Zn in serum of control obese pregnant women (n=10) averaged 2404, 2663, 11.0, 89.0 and 666 μg/l respectively, while in the obese diabetic group (n=11), the corresponding values averaged 2441, 2580, 13.3, 85.1 and 610 μg/l respectively. Activities of antioxidant enzymes such as SOD, GPX and TAO were not significantly different in maternal veins of control and diabetic groups. Varying differences were noted in the case of antioxidant enzyme activities in umbilical blood samples of control and study groups. We conclude that obesity is not associated with significant alterations in antioxidant enzyme status in gestational diabetes and only with relatively minor alterations in status of some essential trace elements.     

The effects of sulfonylurea glyburide on superoxide dismutase, catalase, and glutathione peroxidase activities in the brain tissue of streptozotocin-induced diabetic rat

ObjectivesA member of the second-generation sulfonylureas, glyburide (GLY; glibenclamide) provides an effective therapy for patients with type 2 diabetes. It stimulates pancreatic insulin secretion, suggesting that it is effective in the treatment of type 2 diabetes primarily by elevating the circulating insulin levels. However, experimental evidences have indicated that sulfonylureas have also had an extrapancreatic effect, which may directly contribute toward maintaining blood glucose homeostasis during diabetes.MethodsIn this study, we administrated GLY to streptozotocin-induced diabetic rats and determined the effects of such treatment on activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) from brain tissue.Results and DiscussionBrain CAT and GPx activities were not significantly different in the diabetic group compared to controls (P>.05), but the SOD activity was significantly reduced in the diabetic group compared to controls (P<.001). GLY treatment of 4 weeks had restored the SOD and CAT enzyme activities in diabetic rat brain (P<.05). In addition, high blood glucose levels of untreated diabetic rats were decreased following the GLY treatment (P<.01). Administration of GLY to diabetic rats restored the diabetes-induced changes, suggesting that GLY could restore the brain SOD and CAT activities.     

Enhancement of glomerular heme oxygenase-1 expression in diabetic rats

An increase in oxidative stress in diabetic subjects is implicated to play a pivotal role in diabetic vascular complications. In response to oxidative stress, antioxidant enzymes are considered to be induced and protect cellular functions to keep in vivo homeostasis. However, it remains to be clarified whether antioxidant enzymes are induced against oxidative stress especially in renal glomeruli at an early stage of diabetes. To answer this question, we examined the gene expression of a variety of antioxidant enzymes in glomeruli isolated from streptozotocin-induced diabetic rats. The mRNA expression of antioxidant enzymes such as catalase, glutathione peroxidase, and CuZn-superoxide dismutase, was unaltered in glomeruli of diabetic rats and was comparable to control rats. In contrast, the mRNA expression of heme oxygenase-1 (HO-1) was enhanced in glomeruli of diabetic rats as compared with control rats. A treatment with insulin as well as with vitamin E (40 mg/kg body weight every other day, intra-peritoneal injection) normalized the mRNA expression of HO-1 in the glomeruli of diabetic rats. Immunohistochemical analysis revealed that the up-regulated expression of HO-1 protein was localized in glomerular cells of diabetic rats. In conclusion, these results provide the first evidence that among antioxidant enzymes HO-1 expression is preferentially increased in diabetic glomeruli.     

Correction of endothelial dysfunction in diabetic female rats by tetrahydrobiopterin and chronic insulin

Diabetes-induced vascular dysfunction has mainly been studied in males. However, the mechanisms involved may not correspond to those in females. Here we analyzed the effects of tetrahydrobiopterin (BH(4)) and chronic insulin on the physiology of mesenteric arterioles of alloxan-diabetic female rats. The parameters studied were the mesenteric arteriolar reactivity (intravital microscopy), nitric oxide synthase (NOS) activity (conversion of L-arginine to L-citrulline), eNOS gene expression (RT-PCR), NO production (diaminofluorescein), reactive oxygen species (ROS) generation (intravital fluorescence microscopy) and Cu/Zn superoxide dismutase (SOD) activity (spectrophotometry) and gene expression (RT-PCR). The reduced endothelium-dependent vasodilation of diabetic females was corrected by both BH(4) and insulin. NOS activity was decreased by diabetes, but insulin did not correct it. However, NOS expression was not modified by either diabetes or insulin. Arterioles of diabetic rats exhibited lower NO production, which was fully corrected by BH(4) and only partially by insulin. ROS generation was increased in diabetic rats, and both BH(4) and insulin normalized it. Diabetes did not change SOD activity and gene expression. However, insulin increased SOD activity but not its expression. Our data suggest that, similarly to males, endothelial dysfunction in female diabetic rats involves an altered ROS/NO imbalance. In contrast to males, however, insulin does not regulate NOS in the microcirculation of diabetic females.     

桃叶珊瑚苷对糖尿病大鼠线粒体的抗氧化作用

目的 研究桃叶珊瑚苷对链脲佐菌素(STZ)诱导的糖尿病大鼠血糖和线粒体抗氧化能力的影响. 方法 通过STZ腹腔注射建立糖尿病大鼠模型,将其随机分为糖尿病组、STZ低剂量组和STZ高剂量组,并与空白对照组比较.观察桃叶珊瑚苷治疗前后糖尿病大鼠的形态、体质量、血糖、线粒体内脂质过氧化和抗氧化体系的变化. 结果 与空白对照组比较,糖尿病大鼠血糖、MDA显著升高,CAT、GSH-Px、SOD活力显著下降;桃叶珊瑚苷治疗后血糖、MDA显著降低,CAT、GSH-Px、SOD活力显著升高. 结论 桃叶珊瑚苷能显著降低糖尿病大鼠的血糖值,改善线粒体的抗氧化水平,是一种潜在的防治糖尿病药物.     

Oxidant/antioxidant status in men with Behçet’s disease

Behçet’s disease (BD) is a chronic, progressive disorder that affects many systems of the body including the eye. The aim of this study was to assess whether the increase in oxidative stress in the affected tissues is reflected by lipid peroxidation and to check for alterations in antioxidants and antioxidant enzyme activities in patients with BD. Erythrocyte antioxidant potential (AOP), glutathione (GSH) and GSH-dependent enzymes (glutathione peroxidase (GSH-Px), glutathione reductase (GRD) and glutathione-S-transferase (GST), catalase (CAT), Cu–Zn superoxide dismutase (Cu–Zn SOD) activities, malondialdehyde (MDA) and some trace elements (zinc, Zn; copper, Cu; manganese, Mn) levels in men with BD. Erythrocyte CAT, GSH-Px activities, MDA, GSH, AOP and serum Zn values were significantly lower in patients with BD than in the control group. However, erythrocyte Cu–Zn SOD, GRD activities, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and Cu values were significantly higher in patients with BD than in the control group, but GST activity and serum Mn values were unchanged. In conclusion, our results confirm the presence of oxidative stress in patients with BD and suggest that the severity of BD may arise from impaired antioxidant mechanisms. Therapy with antioxidants may lead to the increase in the antioxidant defense system and thus improvement in clinical symptoms.     

Effect of haemodialysis on the oxidative stress and antioxidants in diabetes mellitus

Abstract Oxidative stress has been defined as a loss of counterbalance between free radical or reactive oxygen species (ROS) production and antioxidant systems. It is involved in the pathogenesis of different chronic diseases. High levels of ROS production via different biochemical mechanisms accompany diseases like type 2 diabetes mellitus (DM) and end-stage renal disease (ESRD). Elevated oxidative status and reduced antioxidant defence systems in patients with DM and ESRD accelerate the prevalence of atherosclerosis and other chronic complications. Our aim was to reveal the effects of diabetes and haemodialysis (HD) separately and together on oxidative stress. In our study, we included 20 diabetic (DM) patients with no renal disease, 20 non-diabetic haemodialysis (HD), 20 diabetic haemodialysis (DHD) patients and 20 healthy volunteers. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances (TBARS), oxidative protein damage as indicated by protein carbonyl (PCO) content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) in all patient groups and healthy subjects. We found enhanced oxidative stress in all patient groups due to an increase in lipid peroxidation (TBARS) and increased oxidative protein damage in terms of PCO content and reduced activities of SOD, CAT and GSH-Px. Oxidative stress was more profound in diabetic patients undergoing haemodialysis. We conclude that both diabetes and dialysis increase oxidative stress and their combined effect on oxidative stress is the highest in magnitude as observed in diabetic patients undergoing haemodialysis.     

Antidiabetic effect of S-allylcysteine: effect on thyroid hormone and circulatory antioxidant system in experimental diabetic rats

ObjectiveIt is considered that diabetes mellitus and thyroid disease are the two common endocrine disorders and also suggested that insulin and thyroid hormones influence each other actions. The present study was designed to investigate the effect of the administration of S-allylcysteine (SAC), a sulfur containing amino acid derived from garlic on blood glucose, insulin, HbA1C, total protein, albumin, Thyroid hormone (T3, T4), TSH, TBARS and circulatory antioxidant levels (SOD, CAT, GSH and GPx) in STZ-induced diabetic rats.MethodsSAC was administered orally for 45 days to control and STZ induced diabetic rats. The effects of SAC on glucose, plasma insulin, HbA1C, total protein, albumin, Thyroid hormone, TSH and circulatory antioxidant levels were studied.ResultsThe levels of glucose, TBARS, hydroperoxide and HbA1C were increased significantly whereas the levels of plasma insulin, reduced glutathione, superoxide dismutase, catalase, GSH, GPx, total protein, albumin, Thyroid hormone and TSH were decreased in STZ induced diabetic rats. Administration of SAC to diabetic rats showed a decrease in plasma glucose, TBARS, hydroperoxide and HbA1C. In addition, the levels of plasma insulin, SOD, CAT, GPx, GSH, total protein, albumin, Thyroid hormone and TSH were increased in SAC treated diabetic rats. The effect of SAC was compared with gliclazide, a well-known antioxidant and antihyperglycemic drug.ConclusionFrom these findings, it is indicated that SAC might be acting through activation in the synthesis and/or secretion of circulating thyroid hormones which in turn stimulate the synthesis of insulin.     

Effect of insulin on impaired antioxidant activities in aortic endothelial cells from diabetic rabbits.

The defense system of aortic endothelial cells against oxidative stress was studied in alloxan-induced diabetic rabbits, and the effect of insulin on the antioxidant activities was estimated. Endothelial cells were prepared from 10 diabetic rabbits, 18 diabetic rabbits treated with insulin, and 10 age-matched controls after 17 days of diabetes. These cells were used for the estimation of glutathione (GSH) levels and its related enzyme activities. The antioxidant activities in these endothelial cells from diabetic rabbits were compared with those from control subjects. The concentration of GSH decreased in diabetic rabbits (1.6 +/- 0.2 nmol/mg protein [mean +/- SD] v 3.7 +/- 0.6 nmol/mg protein). Decreases in the activities of Cu, Zn-superoxide dismutase (Cu,Zn-SOD) (62.7 +/- 11.0 U/mg protein v 172.9 +/- 20.2 U/mg protein), catalase (7.6 +/- 2.1 U/mg protein v 12.3 +/- 3.2 U/mg protein), and GSH peroxidase (134.0 +/- 27.0 mU/mg protein v 179.1 +/- 26.2 mU/mg protein) were observed. The activities of other GSH-related enzymes such as GSH S-transferase or GSH reductase did not change in endothelial cells from diabetic rabbits. Most of these antioxidant activities were prevented when diabetic rabbits were treated with insulin (1 to 2 U/kg/d). These antioxidant activities were also determined in the diabetic liver and kidney. Similar decreases in the cellular defense activities and prevention of the decrease in activities by insulin were observed in the diabetic liver, while these antioxidant enzyme activities in the kidney were resistant to diabetic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

糖尿病视网膜组织中自由基防御机能变化的实验研究

观察了糖尿病大鼠在不同病程时视网膜组织中超氧化物歧化酶（ＳＯＤ）、过氧化氢酶（ＣＡＴ）和谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）的活性及脂质过氧化物（ＬＰＯ）水平的变化。结果显示：在各实验时点，糖尿病大鼠视网膜组织中ＳＯＤ和ＣＡＴ活性明显低于对照组，ＬＰＯ水平显著升高，ＳＯＤ／ＬＰＯ和ＣＡＴ／ＬＰＯ明显降低，且随病程延长改变更明显。提示糖尿病大鼠视网膜组织中自由基防御机能明显降低，这种变化可能在糖尿病视网膜病变的发生发展中起重要作用。     

Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome

Previously, we have demonstrated that chronic consumption of a high-fat, high-refined sugar (HFS) diet results in metabolic syndrome which is marked by obesity, insulin resistance, hyperlipidemia, and hypertension in Fischer rats. Metabolic syndrome in this model is associated with oxidative stress, avid nitric oxide (NO) inactivation by reactive oxygen species (ROS), diminished NO bioavailability, and dysregulation of NO synthase isotypes. Although occurrence of oxidative stress and its impact on NO metabolism are well established, the molecular source(s) of ROS in this model is unknown. In an attempt to explore this issue, we measured protein expressions of the key ROS-producing enzyme, NAD(P)H oxidase, and the main antioxidant enzymes, superoxide dismutase (CuZn SOD and Mn SOD), catalase, glutathione peroxidase (GPX), and heme oxygenase-2 (HO-2), in the kidney and aorta of Fischer rats fed an HFS or low-fat, complex-carbohydrate diet for 7 months. In addition, plasma lipid peroxidation product (malondialdehyde) as well as endothelium-dependent and -independent vasorelaxation (aorta rings) was determined. The results showed a significant upregulation of gp91(phox) subunit of NAD(P)H oxidase and downregulations of SOD isoforms, GPX, and HO-2 in the kidney and aorta of the HFS-fed animals. This was associated with increased plasma malondialdehyde concentration and impaired vasodilatory response to acetylcholine, but not the NO donor, Na nitroprusside. The latter findings confirm the presence of oxidative stress and endothelial dysfunction in the HFS-fed rats. Oxidative stress and endothelial dysfunction in the diet-induced metabolic syndrome are accompanied by upregulation of NAD(P)H oxidase, pointing to increased ROS production capacity, and downregulation of SOD isoforms, GPX, and HO-2, the key enzymes in the antioxidant defense system.     

Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat

BACKGROUND: This study investigates the contribution of vitamin supplementation to the efficacy of oral antidiabetic therapy on the reversal of endothelial dysfunction in a model of type-2 diabetes in rat. METHODS: Diabetes was induced by streptozotocin injection to neonatal rats which were breastfed for 4 weeks, then fed 6 weeks with normal food or food supplemented with 2% vitamin E and 4% vitamin C. Some diabetic rats were treated with gliclazide for 6 weeks. Endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside (SNP) were recorded in thoracic aortic rings. Plasma insulin, HbA(1c) and antioxidant vitamins (A, C and E); plasma and aortic malondialdehyde (MDA) levels were determined. RESULTS: Induction of diabetes resulted in decreased body weight and increased blood glucose, plasma insulin and HbA(1c) levels compared to controls. Acetylcholine relaxation was impaired in diabetic aorta, while SNP relaxation remained unchanged. Aortic MDA level was significantly higher, while plasma vitamin levels were lower in diabetic rats. Diminished acetylcholine response, enhanced aortic MDA level and decreased plasma vitamin levels were all restored after gliclazide and/or vitamin therapy. However, vitamin supplementation in control rats significantly impaired acetylcholine relaxations and increased aortic MDA levels. CONCLUSIONS: Apparently, a selective endothelial dysfunction accompanies the imbalance in oxidant/antioxidant status in the type-2 diabetes model of rat and gliclazide and/or vitamin supplementation improves the impairment in diabetic vasculature. However, vitamin supplementation triggers oxidative stress in normal aortic tissue, thereby, leads to endothelial dysfunction; indicating that nutritional extra-supplementation of antioxidant vitamins isn't advisable for normal subjects, although it's beneficial in disease status.     

Lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes

The aim of this study was to evaluate lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes, and then to establish whether moderate doses of nonenzymatic antioxidant vitamin E play a role in the antioxidant defence system in diabetic pregnant rats and their offspring. The study group consisted of 30 normal female Wistar rats, which were given a single dose of streptozotocin (40 mg/kg) and were mated 7 days later. Subsequently, the diabetic animals were divided into two matched groups: the first supplemented with vitamin E (30 mg/100 g chow), and the other fed with a standard diet lacking vitamine E. Controls consisted of 15 pregnant rats. On the first day after delivery, the rats were decapitated and homogenates of maternal liver and uterus as well as neonatal lungs and liver were prepared. Then the following parameters were measured: malondialdehyde (MDA) concentrations in the homogenates and blood serum, glutathione (GSH) levels, the activity of CuZn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glycaemia. The neonates of diabetic rats were smaller than the healthy ones and serum glucose concentration was markedly higher in the diabetic animals. MDA levels were significantly increased, whereas GSH, SOD and GPx were markedly diminished in the diabetic adult rats and their offspring in comparison to the control grouop. In the animals supplemented with α-tocopherol, MDA concentrations were significantly lower, GSH content and SOD activities were markedly elevated most tissues studied, whereas GPx remained unchanged. We conclude that, by monitoring the activity of selected scavenging enzymes, information on ongoing biological oxidative stress and thereby on the fetus/neonate status may be obtained. Our results suggest that diabetic pregnant rats and their neonates are exposed to an increased oxidative stress and that vitamin E supplementation may reduce its detrimental effects. Received: 20 January 2000 / Accepted in revised form: 23 February 2001     

Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C

AIM: To assess the extent of micronutrient and oxidative stress in blood and to examine their linkages with viral loads in chronic hepatitis C patients.METHODS: Hepatitis C virus (HCV)-RNA levels were quantified in the serum from 37 previously untreated patients with chronic hepatitis C. The plasma and erythrocyte micronutrients (zinc, selenium, copper, and iron) were estimated, and malondialdehyde (MDA)contents were determined as a marker to detect oxidative stress. Antioxidant enzymes, superoxide dismutase (SOD),glutathione peroxidase (GPX) and glutathione reductase (GR) activities in blood were also measured. The control group contained 31 healthy volunteers.RESULTS: The contents of zinc (Zn), and selenium (Se)in plasma and erythrocytes were significantly lower in hepatitis C patients than in the controls. On the contrary,copper (Cu) levels were significantly higher. Furthermore,plasma and erythrocyte MDA levels, and the SOD and GR activities in erythrocytes significantly increased in hepatitis C patients compared to the controls. However, the plasma GPX activity in patients was markedly lower. Plasma Se (r= -0.730, P<0.05), Cu (r = 0.635), and GPX (r = -0.675)demonstrated correlations with HCV-RNA loads. Significant correlation coefficients were also observed between HCV-RNA levels and erythrocyte Zn (r = -0.403), Se (r = -0.544), Cu (r = 0.701) and MDA (r = 0.629) and GR (r = 0.441).CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as related anti-oxidative enzymes (GR and GPX) in blood have important impact on the viral factors in chronic hepatitis C. The distribution of these parameters might be significant biomarkers for HCV.     

Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C

AIM: To assess the extent of micronutrient and oxidative stress in blood and to examine their linkages with viral loads in chronic hepatitis C patients. METHODS: Hepatitis C virus (HCV)-RNA levels were quantified in the serum from 37 previously untreated patients with chronic hepatitis C. The plasma and erythrocyte micronutrients (zinc, selenium, copper, and iron) were estimated, and malondialdehyde (MDA) contents were determined as a marker to detect oxidative stress. Antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase (GR) activities in blood were also measured. The control group contained 31 healthy volunteers. RESULTS: The contents of zinc (Zn), and selenium (Se) in plasma and erythrocytes were significantly lower in hepatitis C patients than in the controls. On the contrary, copper (Cu) levels were significantly higher. Furthermore, plasma and erythrocyte MDA levels, and the SOD and GR activities in erythrocytes significantly increased in hepatitis C patients compared to the controls. However, the plasma GPX activity in patients was markedly lower. Plasma Se (R=-0.730, P<0.05), Cu (r=0.635), and GPX (r= -0.675) demonstrated correlations with HCV-RNA loads. Significant correlation coefficients were also observed between HCV-RNA levels and erythrocyte Zn (r=-0.403), Se (r = -0.544), Cu (r= 0.701) and MDA (P=0.629) and GR (r =0.441). CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as related anti-oxidative enzymes (GR and GPX) in blood have important impact on the viral factors in chronic hepatitis C. The distribution of these parameters might be significant biomarkers for HCV.