Dysregulation of hepatic superoxide dismutase, catalase and glutathione peroxidase in diabetes: response to insulin and antioxidant therapies

Recent evidence suggests that impaired antioxidant status is involved in oxidative stress associated with diabetes. The main antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). The aim of the present investigation was to evaluate the activities and protein expression of these antioxidant enzymes in streptozotocin-induced diabetes. Furthermore, the effects of insulin and antioxidant therapy alone and in combination were studied. Male Sprague-Dawley rats were rendered diabetic by streptozotocin administration and randomly assigned to untreated, insulin-treated, antioxidant (vitamin E and C)-treated and insulin plus antioxidant-treated groups. Normal rats fed either a regular diet or the antioxidant (vitamin E and C)-rich diet served as controls. The animals were observed for 4 weeks. Diabetic animals showed marked weight loss, decreased activities of Cu Zn SOD and CAT and normal GPX activity. Additionally, the expression of all antioxidant enzyme proteins was decreased in the diabetic rats compared to the untreated controls. Insulin therapy prevented weight loss and normalized the activities and protein expression of all antioxidant enzymes. Antioxidant therapy in the diabetic rats normalized Cu Zn SOD and GPX protein expression. Combined therapy with insulin and antioxidants normalized all measured antioxidant enzyme protein expression and activities. Thus diabetes-associated reductions in antioxidant enzymes can be ameliorated by insulin and/or antioxidant therapy.     

Antioxidant enzymes and effects of tempol on the development of hypertension induced by nitric oxide inhibition

BACKGROUND: This study analyzed whether hypertension induced by N(omega)-nitro-l-arginine methyl ester (L-NAME) is associated with dysregulation of the main antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase [GPX], and glutathione reductase [GR]) and whether chronic administration of tempol ameliorates this hypertension. METHODS: Four groups of male Wistar rats were used: 1) control rats; 2) rats treated with L-NAME (35 mg/100 mL in drinking fluid); 3) rats treated with tempol (18 mg/100 mL in drinking fluid); and 4) rats treated with L-NAME plus tempol. All treatments were maintained for 6 weeks. Body weight, systolic blood pressure (BP) determined by the tail-cuff method, and heart rate were measured once per week. At the end of the experimental period, direct BP and morphologic, metabolic, plasma, and renal variables were measured. Enzymatic activities were measured in the kidney (cortex and medulla) and heart (right and left ventricles). RESULTS: Rats with L-NAME-induced hypertension showed increased copper-zinc (Cu-Zn) SOD activity in the renal cortex and medulla and the left and right ventricles, which was reduced by tempol administration. The manganese (Mn) SOD activity was increased by L-NAME and reduced by tempol in the renal cortex but was unchanged in other tissues. Catalase activity was not affected by L-NAME or tempol treatments in any tissue. Both GPX and GR activities were increased by L-NAME and reduced by tempol in the renal cortex and medulla but were not affected in the ventricles. Tempol reduced BP and total urinary excretion of 8-hydroxy-2'-deoxyguanosine in L-NAME-treated animals but did not affect either variable in controls. CONCLUSIONS: We conclude that L-NAME-induced hypertension is associated with an upregulation of antioxidant SOD, GPX, and GR activities. Moreover, the results indicate that tempol attenuates hypertension on nitric oxide-deficient rats and that oxidative stress participates in the established phase of this type of hypertension.     

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.     

Overexpression of inducible nitric oxide synthase in the kidney of the spontaneously hypertensive rat

In kidney, nitric oxide (NO) produced by nitric oxide synthase (NOS) regulates sodium and water excretion and renal medullary blood flow. However, excessive NO production causes nitrative damage and oxidative stress. Since oxidative stress may be linked to hypertension, we examined the expression and activity of inducible NOS (iNOS) in the kidney of the spontaneously hypertensive rat (SHR) and compared our findings to control normtotensive Wistar Kyoto (WKY) rat. Compared with WKY rat, there was significant (p < .05) overexpression (by 96%) and increased (2-fold) activity of iNOS in the cortex but not in the outer medulla, of SHR kidney; in the inner medulla, there was a 6.9-fold increase in iNOS activity in SHR. Increased expression (by 104%) and activity (3.3-fold) of iNOS was specifically observed in proximal tubules (PTs) of the cortex, accompanied by higher (2-fold) tissue nitrite levels. Although certain antioxidant enzymes such as catalase and Mn-superoxide dismutase were overexpressed, glutathione peroxidase was underexpressed in SHR PTs. Overexpression of the inducer of the iNOS promoter, nuclear factor-kappaB (NF-kappaB), with elevated nitrotyrosinylated proteins, further confirmed an elevated state of iNOS-induced oxidative stress in SHR kidneys, possibly signifying its role in the maintenance of essential hypertension seen in these animals.     

Antioxidant enzymes in hypertensive and hypertriglyceridemic rats: effect of gender

In a model of hypertensive and hypertriglyceridemic rats (HTG), in which oxidative stress is increased, the influence of gender upon activities of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) was investigated. Statistically significant differences between antioxidant enzyme activities and treatment with relation to gender were analyzed. Weanling Wistar rats were given normal rat chow and either tap water for control group or 30% sucrose solution for HTG group, for 5-6 months. At the end of the experimental period, blood pressure was significantly higher in both male and female HTG groups, but males showed higher values than females. Serum, heart, kidney, and liver were obtained to determine antioxidant enzyme activities. Activities of CAT and GPX tended to be higher in male animals. A larger number of significant changes in enzyme activities associated with gender appears in HTG than in controls, which indicates the harmful effect of the treatment.     

Age-related changes in renal expression of oxidant and antioxidant enzymes and oxidative stress markers in male SHR and WKY rats

Oxidative stress has been hypothesized to play a role in aging and age-related disorders, such as hypertension. This study compared levels of oxidative stress and renal expression of oxidant and antioxidant enzymes in male normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) at different ages (3 and 12 months). In the renal cortex of 3-month old SHR increases in hydrogen peroxide (H₂O₂) were accompanied by augmented expression of NADPH oxidase subunit Nox4 and decreased expression of antioxidant enzymes SOD1 and SOD3. A further increase in renal H₂O₂ production and urinary TBARS was observed in 12-month old WKY and SHR as compared with 3-month old rats. Similarly, expressions of NADPH oxidase subunit p22^phox, SOD2 and SOD3 were markedly elevated with age in both strains. When compared with age-matched WKY, catalase expression was increased in 3-month old SHR, but unchanged in 12-month old SHR. Body weight increased with aging in both rat strains, but this increase was more pronounced in WKY. In conclusion, renal oxidative stress in 12-month old SHR is an exaggeration of the process already observed in the 3-month old SHR, whereas the occurrence of obesity in 12-month old normotensive rats may partially be responsible for the age-related increase in oxidative stress.     

Catalase,superoxide dismutase,and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication

Background. The aim of this study was to determine the possible relationship between the activity of three different antioxidant enzymes — peroxidase superoxide dismutase, catalase, and glutathione peroxidase — and carbon tetrachloride-induced injury. Methods. Male Wistar rats weighing 200–250?g were used in the experiments. Rats of the experimental groups were given carbon tetrachloride 0.5?ml/kg i.p. in olive oil (5?mmol/kg body mass) for 1 or 3 days. Control group rats were injected with olive oil only for the same period. Brain, liver, kidney, and heart supernatants were used for measurement of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) activities. Results. No statistically significant changes in SOD and GPX activities were observed in the liver after CCl₄ administration, but catalase activity was significantly increased after 24?h and remained at that level during the course of the study. In the brain, SOD and catalase activities decreased after 24?h of experiment, but GPX activity statistically significantly increased at all time points studied. Increased activities of SOD, catalase, and GPX were found in heart after CCl₄ intoxication. The CCl₄ injection in our experiment caused a reduction of SOD and catalase activities and increased GPX activity in the kidney. Conclusions. The results suggest that change in antioxidant enzyme activities may be relevant to the ability of the liver and other investigated organs to cope with oxidative stress during CCl₄ poisoning.     

Melatonin administration differentially affects age-induced alterations in daily rhythms of lipid peroxidation and antioxidant enzymes in male rat liver

A central clock/pacemaker, suprachiasmatic nuclei of the hypothalamus coordinates and entrains circadian oscillations in the peripheral tissues such as the liver, kidney, heart, lungs etc. called peripheral clocks. These also have endogenous circadian oscillations. The circadian rhythms of antioxidants present in cytosol signify redox state of the cell during day/night cycle. The liver has a major impact on homeostasis through its control on serum protein composition and plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products and undergoes substantial changes in structure and function upon aging. In present study, the temporal patterns of oxidative stress indicators in liver were studied. Daily rhythms of lipid peroxidation end products, reduced glutathione (GSH), oxidized glutathione (GSSG) and antioxidant enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were studied in liver at variable time points (Zeitgeber Time (ZT) 0, 6, 12 and 18) in three age groups: 3 (adult), 12 and 24?months old male Wistar rats. There was increase in oxidative stress in 12 and 24?months old rats indicated through a significant increase in lipid peroxidation, decrease in GSH/GSSG ratio and antioxidant enzyme activities. In 3?months old rats, lipid peroxidation was maximum at ZT-12 whereas GSH, SOD and CAT activities were minimum at ZT-12. The maximum level in 24?h i.e., acrophases of lipid peroxidation, GPx, SOD and CAT activities in liver cell free extracts altered upon aging. As melatonin, messenger of darkness, an endogenous synchronizer of rhythm, an antioxidant and an antiaging drug, declines with aging we studied the effects of melatonin on activities of these antioxidant enzymes in aging rats. Melatonin administration resulted in differential restoration of acrophases, amplitude, mean as well as daily rhythms of lipid peroxidation and antioxidants in liver of 12 and 24?months old rats.     

Effects of probucol on changes of antioxidant enzymes in adriamycin-induced cardiomyopathy in rats

OBJECTIVE: The clinical usefulness of doxorubicin (adriamycin, ADR) is restricted by the risk of developing congestive heart failure. Probucol has been reported to completely prevent ADR cardiomyopathy without interfering with its antitumor effects. The current study investigated the effects of ADR and probucol on antioxidant enzyme gene expression during adriamycin-induced cardiomyopathy in a rat model. METHODS: The mRNA abundance by Northern and immunoreactive protein levels by Western blotting of myocardial antioxidant enzymes, glutathione peroxidase (GSHPx), manganese superoxide dismutase (MnSOD) and catalase (CAT) were examined in relation to the enzyme activities in hemodynamically assessed control and treated animals. RESULTS: At 3 weeks post-treatment duration, ADR caused heart failure which was prevented by probucol. MnSOD mRNA abundance as well as protein levels were depressed by ADR treatment by 45% and 20%, respectively, and this change was prevented by probucol. However, the mRNA and protein levels of GSHPx and CAT were not significantly changed by ADR or probucol. ADR had no effect on SOD activity but this enzyme activity was increased by probucol and probucol plus ADR. GSHPx enzyme activity was decreased and oxidative stress as indicated by TBARS was increased by ADR and these changes were also modulated by probucol. CONCLUSION: An increase in oxidative stress, GSHPx inactivation and MnSOD downregulation during ADR cardiomyopathy were prevented by probucol treatment.     

Erythrocyte antioxidant enzymes and blood pressure in relation to overweight and obese Thai in Bangkok

The specific activities of antioxidant enzymes, [eg superoxide dismutases (SOD), glutathione peroxidase (GPX) and catalase (CAT)], anthropometric measurements, including waist/hip ratio of 48 male and 167 female overweight persons (body mass index (BMI) > or = 25.0 kg/m2) compared with a 26 male and 80 female control group (BMI = 18.5-24.9 kg/m2) of Thai volunteers who attended the Out-patient Department, General Practice Section, Rajvithi Hospital, Bangkok, for a physical check-up during March-October, 1998, were investigated. There was a slightly significant difference between the median age of the sexes. The medians of height, weight, and waist/hip ratio in males were significantly higher than those in female overweight and obese subjects. The median of arm circumference (AC), mid arm muscle circumference (MAMC) in males was significantly higher than those in female overweight and obese subjects (p < 0.05). The prevalences of hypertension based on systolic and diastolic blood pressure of > or = 160/> or = 95 mmHg, were 8.3% and 37.5% for males and 5.4% and 18.6% for females, respectively. There was no significant difference between the median of antioxidant enzymes (SOD, GPX and CAT) between the sexes. No significant differences in the antioxidant enzymes in male overweight/obese persons and normal controls were presented, whereas antioxidant enzymes in female overweight/obese persons were statistically lower than in control females (p < 0.05). A significantly higher SOD, GPX, and CAT status was observed in normal subjects compared with overweight/obese subjects (p < 0.01). A higher prevalence of SOD < or = 2,866 U/gHb, GPX (< or = 15.96 U/gHb in females was found, compared with males. A high percentage of lower catalase (CAT < or = 19.2x10(4) IU/gHb) was found in both sexes (64.5% in males and 64.5% in females). In obese subjects (BMI > or = 30.0 kg/m2), there were significantly positive relationships between systolic and diastolic blood pressure, systolic blood pressure and waist/hip ratio, and SOD could be related to weight, BMI as well as GPX and CAT, whereas the opposite result was observed for age and SOD.     

Melatonin reduces oxidative stress in erythrocytes and plasma of senescence-accelerated mice

It has been suggested that oxidative stress is a feature of aging. The goal of the present study was to assess the oxidant effects related to aging and the protective role of exogenous melatonin in senescence-accelerated mice (SAMP8). Two groups of SAMP8 mice (males and females) were compared with their respective control groups of SAMR1 mice (senescence-resistant inbred strain) to determine their oxidative status without melatonin treatment. Four other groups of the same characteristics were treated with melatonin (10 mg/kg/day) in their drinking water. The melatonin concentration in the feeding bottles was titrated according to water consumption and body weight (i.e. 0.06 mg/mL for 30 g of body weight and 5 mL/day of water consumption). The treatment began when animals were 1-month old and continued for 9 months. When mice were 10-month old, they were anesthetized and blood was obtained. Plasma and erythrocytes were processed to examine oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), and hemolysis. The results showed greater oxidative stress in SAMP8 than in SAMR1, largely because of a decrease in GSH levels and to an increase in GSSG and TBARS with the subsequent induction of the antioxidant enzymes GPX and GR. Melatonin, as an antioxidant molecule, improved the glutathione-related parameters, prevented the induction of GPX in senescent groups, and promoted a decrease in SOD and TBARS in almost all the groups.     

Regulation of key antioxidant enzymatic systems in the sheep endometrium by ovarian steroids

Reactive oxygen species (ROS) and their control by antioxidant enzymes are involved in the physiology of the female reproductive system. Thus, it is important to understand the regulation of key antioxidant enzymatic pathways. The roles of estrogen and progesterone in regulating the physiological functions of the endometrium have become central dogma. We examined the effects of ovarian steroids on superoxide dismutases (SOD1 and SOD2), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GSR) activities in the aglandular caruncular and glandular inter-caruncular endometrial tissues of ovariectomized (OVX) ewes and in OVX ewes treated with estradiol (E2), progesterone (P4), or both hormones according to schedules designed to produce physiological changes of these hormones during the estrous cycle. The activities SOD2, CAT, GPX and GSR in both endometrial tissues were unaffected by P4 treatment. The activity of SOD1 in the aglandular tissue was unaffected by P4 treatment, however this treatment decreased SOD1 activity in the glandular tissue (P < 0.01). Treatment with E2, either alone or in combination with P4, decreased SOD1 (P < 0.01), CAT (P < 0.01) and GPX (P < 0.05) activities in both endometrial tissues. The activity of GSR decreased only in the glandular tissue (P < 0.05) after E2 treatment, either alone or in combination with P4. No change in SOD2 activity was detected in both endometrial tissues after administration of E2, P4 or both hormones. This study provides the first firm evidence for the role of ovarian steroid hormones in the regulation of the activities of key antioxidant enzyme in the endometrium of female mammals.     

Markers of oxidative stress and erythrocyte antioxidant enzyme activity in older men and women with differing physical activity

The aim of the present study was to examine the relationship between markers of oxidative stress and erythrocyte antioxidant enzyme activity and physical activity in older men and women. The present study included 481 participants (233 men and 248 women) in the age group 65–69 years (127 men and 125 women) and in the age group 90 years and over (106 men and 123 women). The classification of respondents by physical activity was based on answers to the question if, in the past 12 months, they engaged in any pastimes which require physical activity. The systemic oxidative stress status was assessed by measuring plasma iso-PGF2α and protein carbonyl concentration as well as erythrocyte antioxidant enzymes activity, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The concentration of plasma iso-PGF2α and protein carbonyls (CP) was lower in groups of younger men and women compared to the respective older groups. In all examined groups, physical activity resulted in decrease of these oxidative stress markers and simultaneously caused adaptive increase in the erythrocyte SOD activity. Additionally, in active younger men CAT, GPx, and GR activities were higher than in sedentary ones. In conclusion, oxidative stress increase is age-related, but physical activity can reduce oxidative stress markers and induce adaptive increase in the erythrocyte antioxidant enzyme activity, especially SOD, even in old and very old men and women.     

Byproducts of oxidative protein damage and antioxidant enzyme activities in plasma of patients with different degrees of essential hypertension

Despite evidence that essential hypertension (EH) is a state of increased oxidative stress, the data on oxidative protein modifications is lacking. Besides, the role of extracellular antioxidant enzymes in EH has not been systematically studied. Study was performed in 45 subjects with EH and 25 normotensive controls. Patients were divided into three groups according to the 2003 ESH/ESC guidelines (grade 1-3). Plasma protein reactive carbonyl derivatives (RCD) and SH-groups (as byproducts of oxidative protein damage) as well as antioxidant enzyme activities superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase were studied spectrophotometrically and correlated with blood pressure (BP). RCD levels were increased in EH patients compared to controls and correlated significantly with both systolic blood pressure (SBP) (r = 0.495, P<0.01) and diastolic blood pressure (DBP) (r = 0.534, P<0.01). Plasma SH-groups content was significantly lower in all patients with EH, with no correlation with BP. SOD and catalase activity in patients with grade 1 EH were similar to that of controls. Patients with grade 2 and 3 of EH had lower SOD and catalase activity. However, significant correlation with SBP and DBP was observed for catalase only (r = -0.331; P<0.05 and r = -0.365; P<0.05, respectively). EH patients exhibited higher plasma GPX activity compared to those in controls, and it correlated with SBP (r = 0.328; P<0.05). The results presented show that increased oxidative protein damage is present in all grades of EH. In mild hypertension extracellular antioxidant enzyme activities are not decreased, suggesting they are probably not critical in early EH, but could be important in moderate to severe EH.     

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.     

Evidence for oxidative stress in tissues derived from succinate semialdehyde dehydrogenase-deficient mice

Summary Animal models of inborn errors of metabolism are useful for investigating the pathogenesis associated with the corresponding human disease. Since the mechanisms involved in the pathophysiology of succinate semialdehyde dehydrogenase (SSADH) deficiency (Aldh5a1; OMIM 271980) are still not established, in the present study we evaluated the tissue antioxidant defences and lipid peroxidation in various cerebral structures (cortex, cerebellum, thalamus and hippocampus) and in the liver of SSADH-deficient mice. The parameters analysed were total radical-trapping antioxidant potential (TRAP) and glutathione (GSH) levels, the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as thiobarbituric acid-reactive substances (TBARS). We first observed that the tissue nonenzymatic antioxidant defences were significantly reduced in the SSADH-deficient animals, particularly in the liver (decreased TRAP and GSH) and in the cerebral cortex (decreased GSH), as compared to the wild-type mice. Furthermore, SOD activity was significantly increased in the liver and cerebellum, whereas the activity of CAT was significantly higher in the thalamus. In contrast, GPx activity was significantly diminished in the hippocampus. Finally, we observed that lipid peroxidation (TBARS levels) was markedly increased in the liver and cerebral cortex, reflecting a high lipid oxidative damage in these tissues. Our data showing an imbalance between tissue antioxidant defences and oxidative attack strongly indicate that oxidative stress is involved in the pathophysiology of SSADH deficiency in mice, and likely the corresponding human disorder. Competing interests: None declared References to electronic databases: Succinic semialdehyde dehydrogenase (SSADH) deficiency, OMIM 271980.     

Effect of quercetin on galactose-induced hyperglycaemic oxidative stress in hepatic and neuronal tissues of Wistar rats

Abstract In recent times there has been great demand for natural products that have possible preventive action against diabetes and its secondary complications. Keeping this in mind, this study was undertaken to investigate the influence of the flavonoid, quercetin, on oxidative stress markers and the antioxidant defence system of hepatic and neuronal tissues from galactose-induced hyperglycaemic rats. Weanling male Wistar rats were treated with 30% galactose in AIN 93 diet (group B, n=8) to induce hyperglycaemia. Control rats received normal Stock AIN 93 diet (group A, n=8). The third set of rats received group B diet with quercetin at 400 mg/100 g diet (group C, n=8). Glucose levels and body weights were measured on a weekly basis for four weeks to monitor the hyperglycaemia induced by galactose feeding. Parameters involved in the pathogenesis of galactose-induced hyperglycaemia, which included organosomatic index, protein content, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), tryptophan fluorescence, content of protein carbonyls, prooxidant malonaldehyde (MDA) and glutathione (GSH) in hepatic and neuronal tissues were determined at the end of the fourth week. The study suggest that quercetin counters the pro-oxidant effects of galactose-induced hyperglycaemic stress, as there was a significant reversal of changes with respect to body weights, organosomatic index of hepatic and neuronal tissues, lipid peroxidation, protein carbonyl content, reduced glutathione and activities of antioxidant enzymes. In addition, treatment with quercetin appears to reduce the osmotic stress induced by hyperglycaemia, as assessed by polyol pathway enzyme aldose reductase. These results imply that inclusion of quercetin in the diet controls, to some extent, galactose-induced hyperglycaemia and its attendant complications.     

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.     

Long-term food restriction attenuates age-related changes in the expression of renal aldosterone-sensitive sodium transporters in Wistar-Kyoto rats: a comparison with SHR

In the present study we hypothesized that age-associated changes in the renal aldosterone/mineralocorticoid receptor (MR) system may differ between normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). In WKY, body mass index significantly increased with age. Fat mass may operate as a confounding factor; therefore, WKY (WKY-FR) was pair-fed with SHR. Pair-feeding resulted in a 14% body weight reduction at the age of 52 weeks in WKY-FR. Renal oxidative stress was increased in aged WKY and SHR. Aged WKY and SHR had increased MR functionality, which correlated positively with increased plasma aldosterone levels, nuclear MR content and abundance of aldosterone effectors in the renal medulla. In contrast, decreases in nuclear MR content were observed in the renal cortex of both strains with aging. When compared to aged SHR, aged WKY-FR had decreased plasma aldosterone levels and decreased activation of the aldosterone/MR system in the renal medulla. Increases in renal oxidative stress and plasma aldosterone in aged WKY, to levels observed in SHR, were not sufficient to result in sustained increases in blood pressure. In conclusion, activation of the aldosterone/MR system is intensified by aging in SHR, whereas increases in body fat mass in WKY associate with hyperaldosteronism and oxidative stress.     

Antioxidant and hepatoprotective effects of Ginkgo biloba phytosomes in carbon tetrachloride-induced liver injury in rodents.

AIM: The protective effects of Ginkgo biloba phytosomes (GBP) on carbon tetrachloride (CCl4)-induced hepatotoxicity and the probable mechanism(s) involved in this protection were investigated in rats. METHODS: Liver damage was induced in Wistar rats by administering a 1:1 (v/v) mixture of CCl4 and olive oil (1 ml/kg, i.p.) once daily for 7 days. GBP at 25 mg/kg and 50 mg/kg, i.p. and reference drug silymarin (200 mg/kg, p.o.) were administered for 10 days to CCl4-treated rats, this treatment beginning 3 days prior to the commencement of CCl4 administration. The degree of protection was evaluated by determining the marker enzymes (SGOT, SGPT and SALP), albumin (Alb) and total proteins (TP). Further, the effects of GBP on lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) were estimated in liver homogenates to evaluate antioxidant activity. RESULTS: GBP (25 and 50 mg/kg) and silymarin elicited significant hepatoprotective activity by decreasing the activities of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPX, GR, Alb and TP in a dose-dependent manner. CONCLUSION: The present findings indicate that the hepatoprotective effects of GBP against CCl4-induced oxidative damage may be due to its antioxidant and free radical-scavenging activity.