Protective effect of zinc supplementation on blood antioxidant defense system in rats exposed to cadmium

The aim of this study was to assess the effects of subchronic exposure to cadmium (Cd) on the antioxidant defense system of red blood cells (RBCs) and lipid peroxide concentration in the plasma, as well as the possible protective role of zinc (Zn). For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl₂, administered in five doses (each of 0.4 mg Cd/kg BW) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg BW, i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl₂, administered in doses of 0.8 mg Zn/kg BW, giving a total dose of 4 mg Zn/kg BW, i.p.; a control group received 0.5 mL of physiological saline in an identical manner.

It was shown that exposure to Cd induced a significant decrease (p<0.05) in superoxide dismutase (Zn/Cu SOD) and catalase (CAT) activities in RBCs. Increased lipid peroxide concentration, measured by thiobarbituric acid reactive substances (TBARS), was also observed in the plasma of cadmium-exposed rats. Cd had no effect on glutathione peroxidase (GSH-Px) activity. Zn administration had a beneficial effect on the Cd-induced decrease in Zn/Cu SOD activity (p<0.05) but not on CAT activity. Animals receiving Cd and Zn simultaneously had significantly (p<0.05) lower concentrations of lipid peroxides than rats exposed to Cd alone. Our results indicate that Cd causes oxidative stress and that Zn supply in conditions of exposure to Cd can partially protect against Cd-induced oxidative stress.     

Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective effect of selenium

The effects of selenium (Se) on antioxidant defense system in liver and kidneys of rats with cadmium (Cd)-induced toxicity were examined. Cd exposure (15 mg Cd/kg b.m./day as CdCl(2) for 4 weeks) resulted in increased lipid peroxidation (LP) in both organs (p<0.005 and p<0.01). Vitamin C (Vit C) was decreased in the liver (p<0.005), whereas vitamin E (Vit E) was increased in the liver and kidneys (p<0.005 and p<0.05) of Cd-exposed animals. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were decreased in both tissues (p<0.05 and p<0.005), whereas catalase (CAT) activity was decreased only in liver (p<0.005). Glutathione S-transferase (GST) increased in both tissues (p<0.005 and p<0.01). Treatment with Se (0.5 mg Se/kg b.m./day as Na(2)SeO(3) for 4 weeks) significantly increased liver and kidneys SOD and GSH-Px activities (p<0.05 to p<0.005), as well as CAT and GST activities only in the liver (p<0.01). In animals exposed to Se, both the concentrations of Vit C (p<0.01) and Vit E (p<0.005) were increased in both tissues. Co-treatment with Se resulted in reversal of oxidative stress with significant decline in analyzed tissues Cd burden. Our results show that Se may ameliorate Cd-induced oxidative stress by decreasing LP and altering antioxidant defense system in rat liver and kidneys and that Se demonstrates the protective effect from cadmium-induced oxidative damage.     

Effects of fish oil and vitamin E on the antioxidant defense system in diet-induced hypercholesterolemic rabbits

This study was designed to investigate the effects of fish oil and vitamin E on the antioxidant defense system in hypercholesterolemic rabbits. A high fat and cholesterol diet, with or without supplement by fish oil and/or a vitamin E supplement, was fed to rabbits for 6 weeks. Compared to the reference diet of regular laboratory rabbit chow, a high fat and cholesterol-enriched diet increased atheroma formation, plasma lipid and peroxide levels, decreased blood glutathione levels, and reduced plasma glutathione reductase, glutathione peroxidase, and catalase activities. Fish oil supplementation significantly reduced atheroma and increased glutathione reductase and glutathione peroxidase activities and blood glutathione levels, but increased plasma lipid peroxide levels. Vitamin E supplementation of the fish oil diet enhanced the beneficial effects by increasing glutathione reductase activity and decreasing peroxide levels. These results indicate that a high fat and cholesterol diet attenuates blood glutathione levels and plasma antioxidant enzyme activities, which may account for some of its atherogenic properties. Consumption of fish oil enhances antioxidative defenses against the oxidative stress imposed by hypercholesterolemia, and vitamin E further enhances these beneficial effects.     

Effect of vitamin E supplementation on diabetes induced oxidative stress in experimental diabetes in rats

Diabetes induced by streptozotocin (50 mg/kg body wt, i.p.) in the rats substantially increased the plasma glucose and malondialdehyde levels along with corresponding decrease in the antioxidants levels. Supplementation of vitamin E (200 mg/kg body wt., ip) for 5 weeks resulted in non-significant decrease in the blood glucose levels but plasma malondialdehyde levels were reduced to below normal levels. Plasma vitamin E, vitamin C, uric acid and red blood cell glutathione levels were also restored to near normal levels on vitamin E supplementation to diabetic rats as compared to control (diabetic) rats. The activities of antioxidant enzymes, catalase (EC 1.11.1.6), glutathione peroxidase (GSHPx EC 1.11.1.9), and glutathione reductase (GR EC 1.6.4.2) were also concomitantly restored to near normal levels by vitamin E supplementation to diabetic rats. The results clearly demonstrated that vitamin E supplementation augments the antioxidant defense mechanism in diabetes and provides evidence that vitamin E may have a therapeutic role in free radical mediated diseases.     

Role of calcium in AMF-mediated alleviation of the adverse impacts of cadmium stress in Bassia indica [Wight] A.J. Scott

The aim of this study was to evaluate cadmium stress induced changes in the growth, lipid peroxidation and antioxidant activity of Bassia indica associated with arbuscular mycorrhizal fungi (AMF) and their amelioration by calcium application. Cadmium stress can cause alterations in the physiological and biochemical processes in plants. A calcium application combined with an AMF treatment resulted in the reduction of lipid peroxidation and the production of hydrogen peroxide, thereby mediating the mitigation of cadmium induced oxidative stress. The activity of antioxidant enzymes increased with cadmium application, whereas AMF inoculation combined with a calcium application further enhanced their activity. An increase in the content of non-enzymatic antioxidants such as ascorbate, reduced glutathione (GSH), oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO) in AMF-inoculated and calcium-treated plants further suggests their role in strengthening the antioxidant defense system that results in maintained growth. The application of calcium combined with the AMF treatment caused a significant reduction in lipid peroxidation and in the production of hydrogen peroxide, thereby mediating the mitigation of the cadmium induced oxidative stress. Increased proline accumulation was clearly evident in stressed plants, and the calcium application as well as the AMF inoculation further induced proline synthesis, thereby providing efficient protection against cadmium stress by increasing the maintenance of the systemic resistance criteria.     

Effect of radiotherapy and chemoradiotherapy on circulating antioxidant system of human uterine cervical carcinoma

Circulating lipid peroxide, antioxidant components and the activities of defense enzymes were estimated in uterine cervical carcinoma patients (before and after radiotherapy and radiotherapy combined chemotherapy) and compared with controls. Some of the antioxidant components such as glutathione, vitamin E and selenium are reduced in cervical cancer. The reduced levels of vitamin E and glutathione were normalized after treatment. Erythrocyte lipid peroxide (E-LPx) and erythrocyte membrane lipid peroxide (EM-LPx) levels were found to be increased in all the stages of uterine cervical carcinoma. The important antioxidant enzymes such as erythrocyte superoxide dismutase (E-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) were found to be decreased in uterine cervical carcinoma. These altered biochemical parameters were reversed to normal, of course with varied degree after different mode of therapy. Significant normalization was observed in Type 11 chemoradiotherapy.     

Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction

The present study has been carried out to investigate the role of taurine (2-aminoethanesulfonic acid), a conditionally essential amino acid, in ameliorating cadmium-induced renal dysfunctions in mice. Cadmium chloride (CdCl₂) has been selected as the source of cadmium. Intraperitoneal administration of CdCl₂ (at a dose of 4 mg/kg body weight for 3 days) caused significant accumulation of cadmium in renal tissues and lessened kidney weight to body weight ratio. Cadmium administration reduced intracellular ferric reducing/antioxidant power (FRAP) of renal tissues. Levels of serum marker enzymes related to renal damage, creatinine and urea nitrogen (UN) have been elevated due to cadmium toxicity. Cadmium exposure diminished the activities of enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PD) as well as non-enzymatic antioxidant, reduced glutathione (GSH) and total thiols. On the other hand, the levels of oxidized glutathione (GSSG), lipid peroxidation, protein carbonylation, DNA fragmentation, concentration of superoxide radicals and activities of cytochrome P450 enzymes (CYP P450s) have been found to increase due to cadmium intoxication. Treatment with taurine (at a dose of 100 mg/kg body weight for 5 days) before cadmium intoxication prevented the toxin-induced oxidative impairments in renal tissues. The beneficial role of taurine against cadmium-induced renal damage was supported from histological examination of renal segments. Vitamin C, a well-established antioxidant was used as the positive control in the study. Experimental evidence suggests that both taurine and vitamin C provide antioxidant defense against cadmium-induced renal oxidative injury. Combining all, results suggest that taurine protects murine kidneys against cadmium-induced oxidative impairments, probably via its antioxidative property.     

Effects of zinc pre-treatment on blood glutathione,serum zinc and kidney histological organisation in male rats exposed to cadmium

The effects of sub-chronic exposure to cadmium (Cd) on the blood glutathione, serum zinc and on the kidney histological organisation in rats as well as the possible protective role of zinc (Zn) are the object of this study. For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl₂, administered in five doses (each of 0.4 mg Cd/kg b.w.) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg b.w., i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl₂, administered in doses of 0.8 mg Zn/kg b.w., giving a total dose of 4 mg Zn/kg b w, i.p.; a control group received 0.5 mL of physiological saline in an identical manner. Intoxication with Cd was followed by a significant decrease in blood glutathione, increase in oxidized glutathione as well as histological damage in kidneys. Pre-treatment with Zn exhibited a protective role against Cd toxicity with a significant decrease in serum zinc content. This fact may be explained by an excessive use of zinc in metallothionein synthesis as a cadmium detoxification agent.     

Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in L-NAME-induced hypertensive rats: a dose-dependence study

We investigated the antihypertensive and antioxidant potential of vanillic acid (VA) in N(ω)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) - treated adult male albino Wistar rats. Treatment of rats with L-NAME (40 mg/kg Bw for 30 days) caused a sustained increase in systolic- (SBP) and diastolic blood pressure (DBP) and significantly decreased the concentration of nitrite/nitrate (NO(x)) in plasma as compared with that in the control. Rats treated with VA restored SBP and DBP to normal level and preserve the plasma NO metabolites concentration. Moreover, VA reduced lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) and significantly restored enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase), non-enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma. To assess the toxicity if any of VA treatment, hepatic and renal function markers were measured. Our results showed that the effect at a dose of 50 mg/kg Bw of VA was more pronounced than that of the other two doses, 25 and 100 mg/kg Bw. These results were supported by histopathology studies. We conclude that VA possesses an antihypertensive and antioxidant activity in L-NAME-induced hypertensive rats.     

Role of carnosine in preventing thioacetamide-induced liver injury in the rat

Carnosine (beta-alanyl-L-histidine) is a dipeptide with antioxidant properties. Free radicals are involved in the pathogenesis of acute liver injury induced by thioacetamide (TAA). In this study, we investigated the effect of carnosine treatment on TAA-induced oxidative stress and hepatotoxicity. Rats were injected intraperitoneally with TAA (500 mg/kg) and carnosine (250 mg/kg, intraperitoneal) was co-administered with TAA. All animals were killed 24 h after injections. TAA administration resulted in hepatic necrosis, significant increases in plasma transaminase activities as well as hepatic lipid peroxide levels. In addition, hepatic antioxidant system was found to be depressed following TAA administration. When carnosine was co-administered with TAA in rats, plasma transaminase activities were found to approach to normal values in rats. Histological findings also suggested that carnosine has preventive effect on TAA-induced hepatic necrosis. Carnosine treatment caused significant decreases in lipid peroxide levels in TAA-treated rats without any changes in enzymatic and non-enzymatic antioxidants except vitamin E in the liver of rats. Our findings indicate that carnosine, in vivo may have a preventive effect on TAA-induced oxidative stress and hepatotoxicity by acting as an non-enzymatic antioxidant itself.     

Protective role of <Emphasis Type="SmallCaps">l</Emphasis>-ascorbic acid on antioxidant defense system in erythrocytes of albino rats exposed to nickel sulfate

In this experimental study, we investigated whether l-ascorbic acid has any influence on the blood antioxidant defense system, lipid peroxidation and hematological parameters of the albino rats exposed to nickel sulfate(NiSO₄).Twenty four adult rats were divided into four groups of six animals in each group. The control rats were untreated and comprised Group I. Group II rats were administered nickel sulfate (2.0 mg/100 g b.wt.; intraperitonially, i.p.). Group II rats were treated orally l-ascorbic acid (50 mg/100 g b.wt.) and Group IV rats were given both nickel sulfate and l-ascorbic acid simultaneously on alternate days until the tenth dose. The hematological parameters were assessed: red blood corpuscle counts, packed cell volume %, hemoglobin concentration, white blood corpuscle counts and platelets count decreased significantly and clotting time increased significantly in nickel treated rats. We also observed increase malondialdehyde (MDA) and decrease glutathione level (GSH) in erythrocytes of nickel treated rats. The activities of erythrocyte antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were significantly increased in rats treated with nickel sulfate. Simultaneously treatment of l-ascorbic acid exhibited a possible protective role on the toxic effect of nickel sulfate on the hematological values, erythrocyte MDA and GSH concentrations as well as antioxidant enzymatic defense system.     

Investigation of Cadmium-Induced Genotoxicity and Oxidative Stress Response in Indian Major Carp,Labeo rohita

We investigated genotoxicity and oxidative stress in the gills of Labeo rohita exposed to 33.6, 67.1, and 100.6 mg L^–1of cadmium chloride at 96 h. Genotoxicity was assessed using single cell gel electrophoresis whereas oxidative stress was monitored through lipid peroxidation induction and antioxidant response parameters, namely reduced glutathione (GSH), glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase (CAT) activities. Significant (p < .05) effect of both concentration and time of exposure was observed on the extent of DNA damage in treated fish. Similarly, malondialdehyde content, level of GSH, and activities of antioxidant enzymes were significantly elevated in treated groups, except CAT. The increased DNA damage and lipid peroxidation (LPO) content along with fluctuation in antioxidant defense system in fish indicated the interaction of cadmium (Cd) with DNA repair processes and production of reactive oxygen species. Thus, Cd is liable for induction of LPO, alteration of antioxidant defenses, and DNA damage in gills of L. rohita.     

Effects of Melothriamaderaspatana leaf extract on antioxidant status in sham-operated and uninephrectomized DOCA-salt hypertensive rats

The present study was designed to investigate the antihypertensive and antioxidant effect of Melothria maderaspatana leaf extract (MME) on sham-operated and DOCA-salt (deoxycorticosterone acetate) induced hypertensive rats. Administration of DOCA-salt significantly increased the systolic (from 127 to 212 mm Hg) and diastolic (from 91 to 174 mm Hg) blood pressure compared to sham-operated control rats, while treatment with MME significantly reduced the systolic (from 212 to 135 mm Hg) and diastolic (from 174 to 96 mm Hg) blood pressure compared to hypertensive control. In DOCA-salt rats, the plasma and tissue concentration of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide (LOOH) significantly increased and administration of MME significantly reduced these parameters towards the levels in sham-operated control. In hypertensive rats, activities of the enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and levels of non-enzymatic antioxidants such as vitamin C, vitamin E and reduced glutathione (GSH) decreased significantly in the plasma and tissues. Administration of MME returned the enzymatic and non-enzymatic antioxidants towards sham-operated control. MME shows both antihypertensive and antioxidant properties in DOCA-salt hypertensive rats and, among the three different doses tested, 200 mg/kg caused the maximum effect.     

Cytoprotective and antioxidant role of diallyl tetrasulfide on cadmium induced renal injury: an in vivo and in vitro study

Cadmium (Cd) is an environmental and industrial pollutant that affects various organs in humans and animals. A body of evidence has accumulated implicating the free radical generation with subsequent oxidative stress in the biochemical and molecular mechanisms of Cd toxicity. Since kidney is the critical target of Cd toxicity, we carried out this study to investigate the effects of diallyl tetrasulfide (DTS), an organosulfur compound derived from garlic on Cd induced toxicity in the kidney of rats and also in the kidney cell line (vero cells). In experimental rats, subcutaneous administration of Cd (3 mg/kg bw/day) for 3 weeks induced renal damage, which was evident from significantly increased levels of serum urea and creatinine with significant decrease in creatinine clearance. A markedly increased levels of lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl contents with significant decrease in nonenzymic antioxidants (total sulphydryl groups, reduced glutathione, vitamin C and vitamin E) and enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase) as well as glutathione metabolizing enzymes (glutathione reductase, and glucose-6-phosphate dehydrogenase) were also observed in Cd intoxicated rats. Coadministration of DTS (40 mg/kg bw/day) and Cd resulted in the reversal of the kidney function accompanied by a significant decrease in lipid peroxidation and increase in the antioxidant defense system. In vitro studies with vero cells showed that incubation of DTS (5-50 microg/ml) with Cd (10 microM) significantly reduced the cell death induced by Cd. DTS at 40 microg/ml effectively blocked the cell death and lipid peroxidation induced by Cd (10 microM) indicating its cytoprotective property. Further, the flow cytometric assessment on the level of intracellular reactive oxygen species using a fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCF-DA) confirmed the Cd induced intracellular oxidative stress in vero cells, which was significantly suppressed by DTS (40 microg/ml). The histopathological studies in the kidney of rats also showed that DTS (40 mg/kg bw/day) markedly reduced the toxicity of Cd and preserved the architecture of renal tissue. The present study suggests that the cytoprotective potential of DTS in Cd toxicity might be due to its antioxidant and metal chelating properties, which could be useful for achieving optimum effects in Cd induced renal damage.     

Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats

Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.     

Influence of some metal concentrations on the activity of antioxidant enzymes and concentrations of vitamin E and SH-groups in the digestive gland and gills of the freshwater bivalve Unio tumidus from the Serbian part of Sava River

We examined whether the freshwater bivalve Unio tumidus from the Sava River can serve as a bioindicator organism for long-term biomonitoring of river ecosystems for the presence of metal pollutants. To this end, we assessed in the digestive glands and gills of mussels, changes in activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), the phase II biotransformation enzyme glutathione-S-transferase (GST)), and changes in the concentrations of the non-enzymatic components of the antioxidant system (vitamin E and sulfhydryl groups (-SH), after exposure to metals in the environment. Mussels were collected at four sites where the concentrations of dissolved metals (Cu, Cd, Zn, Fe, Mn, Hg, Ni, As, Pb) were quantified. Cu, Ni and As exerted concentration-dependent inhibitory effects on CAT and GST activities. Increasing concentrations of Cd promoted increases in GSH-Px activity and -SH concentration. In response to increased Zn concentration GR activity increased whereas Fe promoted decreased enzymatic activity. Negative correlations between the concentrations of Cu and Cd and vitamin E, and a positive correlation between Mn and vitamin E concentrations were detected. The described correlations between components of the antioxidant system and metal levels in the environment reveal a high physiological sensitivity of freshwater mussels to pollution, supporting their use in biomonitoring of metal contamination in river ecosystems.     

Lipid peroxidation and antioxidant status in patients with periodontitis

Our aim was to assess the degree of oxidative stress in patients with periodontitis by measuring their levels of thiobarbituric acid reactive substances (TBARS), enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GSHPx)), and non-enzymatic antioxidants (vitamins E and C, reduced glutathione (GSH)). This study was conducted on 25 adult chronic periodontitis sufferers who were patients in Rajah Muthiah Dental College and Hospital, Annamalai University. The levels of TBARS and non-enzymatic antioxidants, and the activities of enzymatic antioxidants in the patients' plasma, erythrocytes and gingival tissues were assayed using specific colorimetric methods. The periodontitis sufferers had a significantly higher TBARS level than the healthy subjects. In the plasma, erythrocytes, erythrocyte membranes and gingival tissues of the periodontitis sufferers, enzymatic antioxidant activities were found to be significantly higher, whereas the levels of non-enzymatic antioxidants were significantly lower (except for reduced glutathione in the gingival tissues) relative to the parameters found for healthy subjects. The disturbance in the endogenous antioxidant defense system due to over-production of lipid peroxidation products at inflammatory sites can be related to a higher level of oxidative stress in patients with periodontitis.     

Antioxidant defense in centenarians (a preliminary study)

The study was designed to assess the antioxidant defense mechanisms, either enzymatic or non-enzymatic, in a group of sixteen centenarians (one male and fifteen female subjects aged 101 to 105 years) living in the Upper Silesia district (Poland) in order to evaluate the potential role of antioxidant defenses in human longevity. The results of our preliminary study showed that in comparison with young healthy female adults the centenarians had significantly higher red blood cell glutathione reductase and catalase activities and higher, although insignificantly, serum vitamin E level.     

Modulatory effect of sesamol on DOCA-salt-induced oxidative stress in uninephrectomized hypertensive rats

The present study was undertaken to investigate the antihypertensive and antioxidant effects of sesamol on uninephrectomized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Hypertension was induced in surgically single-kidney-removed (left) adult male albino Wistar rats, weighing 180–200 g, by injecting DOCA (25 mg/kg BW) subcutaneously twice a week for 6 weeks, with saline instead of tap water for drinking. Rats were treated with three different doses of sesamol (50, 100 and 200 mg/kg BW) post-orally by gavage daily for 6 weeks. Hypertension was revealed by increased systolic and diastolic blood pressure and the toxicity of DOCA-salt was determined using hepatic marker enzymes, aspartate aminotransferase, alanine aminotransferase, alkaline phospatase and gamma-glutamyl transpeptidase; and, lipid peroxidative markers, thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes were assayed. The activities of enzymatic antioxidants, superoxide dismutase, catalase and glutathione peroxidase and the levels of non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were evaluated in erythrocytes, plasma and tissues. Post-oral administration of sesamol at the dosage of 50 mg/kg BW remarkably decreased systolic and diastolic blood pressure, hepatic marker enzyme activities and lipid peroxidation products and also enhanced the antioxidant activity. The biochemical observations were also supported by histopathological examinations of the rat liver, kidney and heart sections. These results suggest that sesamol possesses antihypertensive and antioxidant effects.     

Cerebral antioxidant status and free radical generation following glutathione depletion and subsequent recovery

This study was aimed to evaluate the oxidative damage, production of reactive oxygen species and the status of antioxidative defenses following cerebral GSH depletion induced by two classical depletors, diethylmaleate (DEM, 3 mmol/kg, i.p.) and phorone (PHO, 4 mmol/kg, i.p.). The treatment decreased (40-43%) brain glutathione levels at 2 h, followed by a partial recovery at 24 h. Cerebral glutathione depletion by these agents increased the levels of superoxide anion and hydroxyl radical at both the time intervals; however, hydrogen peroxide was high at 24 h only. It also produced a dramatic increase in the protein carbonyls at 2 h but not at 24h, without any significant effect on lipid peroxidation and conjugated diene levels. These rats showed a significantly lowered superoxide dismutase activity both at 2 h and 24 h of exposure, as compared to controls. Glutathione depletion enhanced catalase activity markedly at 2 h, followed by some recovery at 24 h. While Se-independent glutathione peroxidase (GPx) and glutathione S-transferase activities were increased at both 2 and 24 h time intervals, Se-dependent GPx and glucose-6-phosphate dehydrogenase were induced at 2 h only. Glutathione depletion decreased ceruloplasmin and vitamin E levels significantly at 2 h. However, ascorbic acid remained unaffected. It may be concluded that an acute cerebral glutathione depletion generates higher levels of reactive oxygen species, which may be responsible for oxidative modification of proteins. Some of these changes appear to recover soon after an activation of a variety of cellular antioxidant defense mechanisms and glutathione restoration. It appears that central nervous system is highly vulnerable to oxidative damage following a moderate glutathione depletion that may result from certain diseases or xenobiotic exposures.