Beneficial effects of Hippophae rhamnoides L. on nicotine induced oxidative stress in rat blood compared with vitamin E

The aim of this study was to determine the effects of Hippophae rhamnoides L. extract (HRe-1) and also vitamin E as a positive control on nicotine-induced oxidative stress in rat blood, specifically alterations in erythrocyte malondialdehyde (MDA) level, activities of some erythrocyte antioxidant enzymes, and plasma vitamin E and A levels. The groups were: nicotine (0.5 mg/kg/d, intraperitoneal, i.p.); nicotine+vitamin E (75 mg/kg/d, intragastric, i.g.); nicotine+HRe-1 (1 ml/kg/d, i.g.); and control group (receiving only vehicles). There were 8 rats per group and the supplementation period was 3 weeks. Nicotine-induced increase in erythrocyte MDA level was prevented by both HRe-1 and vitamin E. Nicotine-induced decrease in erythrocyte superoxide dismutase (SOD) activity was prevented by HRe-1, but not vitamin E. HRe-1 increased the erythrocyte glutathione peroxidase (GSH-Px) activity compared with nicotine and the vitamin E groups. Catalase activity was not affected. Vitamin E supplementation increased plasma vitamin E level. Plasma vitamin A level was higher in both vitamin E and HRe-1 supplemented groups compared with nicotine and control groups. The results suggest that HRe-1 extract can be used as a dietary supplement, especially by people who smoke, in order to prevent nicotine-induced oxidative stress.     

Hippophae rhamnoides attenuates nicotine-induced oxidative stress in rat liver

The effects of vitamin E and Hippophae rhamnoides L. (Elaeagnaceae) extract (HRe-1) on nicotine-induced oxidative stress in rat liver were investigated. Four groups, eight rats each, were used in this study, and the supplementation period was 3 weeks. The groups were: nicotine (0.5?mg/kg/day, intraperitoneal (i.p.)); nicotine plus vitamin E (75?mg/kg/day, intragastric (i.g.)); nicotine plus HRe-1 (250?mg/kg/day, i.g.); and the control group. The malondialdehyde and nitric oxide levels, glutathione peroxidase, glutathione S-transferase, glutathione reductase, superoxide dismutase, and total and non-enzymatic superoxide scavenger activities were measured spectrophotometrically in supernatants of the tissue homogenates. Nicotine increased the malondialdehyde level in liver tissue compared with control. This nicotine-induced increase in lipid peroxidation was prevented by both vitamin E and HRe-1. Superoxide dismutase activity was higher in the nicotine plus vitamin E-supplemented group compared with nicotine and control groups. Glutathione reductase activity was higher in the nicotine group compared with the control group. However, glutathione peroxidase activity in the control group was higher than the levels in the nicotine, and the nicotine plus HRe-1 supplemented groups. The nitric oxide level was higher in the nicotine group compared with all other groups. Total and non-enzymatic superoxide scavenger activities and glutathione S-transferase activity were not affected by any of the treatments. Our results suggest that Hippophae rhamnoides extract as well as vitamin E can protect the liver against nicotine-induced oxidative stress.     

Effects of nicotine and vitamin E on glutathione reductase activity in some rat tissues in vivo and in vitro

Effects of nicotine, and nicotine+vitamin E on glutathione reductase (Glutathione: NADP(+) oxidoreductase, EC 1.8.1.7) activity in the muscle, heart, lungs, testicles, kidney, stomach, brain and liver tissues were investigated in vivo and also in vitro. The groups were: nicotine [0.5 mg/kg/day, intraperitoneal (i.p.)]; nicotine+vitamin E [75 mg/kg/day, intragastric (i.g.)]; and control group (receiving only vehicles). There were eight rats per group and supplementation period was 3 weeks. The results showed that nicotine (0.5 mg/kg, i.p.) inhibited glutathione reductase activity significantly in the liver, lungs, heart, stomach, kidney, and testicles by approximately 61.5%, approximately 65%, approximately 70.5%, approximately 72.5%, approximately 64% and approximately 71.5%, respectively, while it had activated glutathione reductase activity in the brain by approximately 11.8%, and had no effect on the muscle glutathione reductase activity. Vitamin E supplementation prevented this nicotine-induced decrease in glutathione reductase activity in liver, lungs, heart, stomach, and kidney. However, it did not prevent this nicotine-induced decrease in testicles. In vitro studies were also carried out to elucidate the effects of nicotine and vitamin E on glutathione reductase activity. In vitro results correlated well with in vivo experimental results in liver, lungs, heart, stomach, and testicular tissues. These results show that vitamin E administration generally restores the inactivation of glutathione reductase activity due to nicotine administration in various rat tissues in vivo, and also in vitro.     

Antioxidant effect of onion oil (Allium cepa. Linn) on the damages induced by nicotine in rats as compared to alpha-tocopherol

The beneficial effects of onion oil as an antioxidant has been assessed in nicotine administered rats by studying whether the peroxidative damage caused by nicotine can be effectively combated with the onion oil and the effects compared to vitamin E, a highly efficient antioxidant. Lipid peroxidation products and antioxidant defence system have been studied in liver, lungs, and heart. The rats were injected with nicotine (0.6 mg/kg body wt.) and simultaneously given onion oil (100 mg/kg body wt.) or vitamin E (100 mg/kg body wt.) for 21 days. Concentration of free fatty acids, TBA reactive substances (TBARS), conjugated dienes and hydroperoxides were significantly increased in the tissues of nicotine treated rats as compared to normal rats. Onion oil supplemented to nicotine treated rats showed increased resistance to lipid peroxidation and the effect was near to that of vitamin E fed rats. The activity of catalase and superoxide dismutase decreased in nicotine treated rats. Antioxidants-glutathione content, vitamin C and retinol showed no significant difference but liver vitamin E content significantly decreased in nicotine treated rats. On onion oil or vitamin E supplementation, the concentration of antioxidants were significantly raised in all the tissues studied, however, a significantly increased concentration of glutathione, vitamin E and retinol was noticed in vitamin E+nicotine treated rats. Thus, these results indicate that onion oil is an effective antioxidant against the oxidative damage caused by nicotine as compared to vitamin E.     

Amelioratory effect of Andrographis paniculata Nees on liver, kidney, heart, lung and spleen during nicotine induced oxidative stress

The ameliorative properties of bioactive compound andrographolide (ANDRO), aqueous extract of Andrographis paniculata (AE-AP) and vitamin E (vit.E) were tested against nicotine induced liver, kidney, heart, lung and spleen toxicity. A group of male Wistar rats were intraperitoneally administered vehicle, nicotine (1 mg/kg body weight/day), nicotine + ANDRO (250 mg/kg body weight/day), nicotine + AE-AP (250 mg/kg body weight/day) and nicotine + vit.E (50 mg/kg body weight/day) for the period of 7 days. The significantly increased levels of lipid peroxidation, protein oxidation and the decreased antioxidant enzyme status were noted in nicotine treated group as compared to vehicle treated group. ANDRO, AE-AP and vit.E significantly reduced the lipid peroxidation, protein oxidation and increased the antioxidant enzyme status. This indicates A. paniculata and vit.E may act as putative protective agent against nicotine induced tissue injury and may pave a new path to develop suitable drug therapy.     

Effects of vitamin E, vitamin C, and selenium on gastric fundus in cadmium toxicity in male rats

Cadmium (Cd) is a highly toxic metal. It has an indirect role in the generation of various free radicals. Antioxidants such as vitamin E, vitamin C, and selenium are important for preventing the damage caused by reactive oxygen species. This study was undertaken to examine the effect of acute cadmium and/or antioxidants on serum lipid metabolism, tissue glutathione, and lipid peroxidation (LPO) levels, and ghrelin and metallothionein production in the gastric fundus mucosa of rats. Cd (2 mg/kg/day CdCl(2)) was administered to rats for 8 days, intraperitoneally. Vitamin E (250 mg /kg/day) + vitamin C (250 mg/kg/day) + sodium selenate (0.25 mg /kg/day) were administered to rats orally at the same time. The animals were treated by antioxidants 1 h prior to treatment with Cd every day. Gastric tissue homogenates were used for protein and glutathione and LPO levels. Phospholipid and total lipid levels were determined in serum. Gastric fundus sections examined for histopathological changes and by immunohistochemistry for expression of ghrelin and metallothionein. In the group treated with Cd, degenerative changes such as discontinuity in the surface epithelium were observed. The degenerative changes induced by Cd were decreased in the group given vitamin E + vitamin C + selenium. There was no significant change in ghrelin- and metallothionein-immunoreactive cells in fundus mucosa. Stomach glutathione levels insignificantly decreased in the Cd groups, but in the Cd group given antioxidant, stomach glutathione levels were significantly increased. Serum phospholipid and total lipid levels were significantly increased in the Cd groups. On the other hand, treatment with antioxidants reversed these effects. These results indicate that antioxidants partly prevent the toxicity of Cd in rat gastric fundus.     

The effects of erdosteine, N-acetylcysteine and vitamin E on nicotine-induced apoptosis of cardiac cells

This study was conducted to investigate the frequency of apoptosis in rat cardiomyocytes after intratraperitoneal nicotine injection, in order to examine the roles of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha)] in nicotine-induced cardiac damage and to determine the protective effects of three known antioxidant agents (N-acetylcysteine (NAC), erdosteine and vitamin E) on nicotine toxicity in the heart. Female Wistar rats were divided into seven groups, each composed of nine rats: two negative control groups, two positive control groups, one erdosteine-treated group (500 mg kg(-1)), one NAC-treated group (500 mg kg(-1)) and one vitamin E-treated group (500 mg kg(-1)). Nicotine was intraperitoneally injected at a dosage of 0.6 mg kg(-1) for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Heart tissue samples were stained with hematoxylin-eosin for histopathological assessments. Apoptosis level in cardiomyocytes was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF-alpha in cardiomyocytes and heart MPO activity were evaluated by immunohistochemistry. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced cardiomyocyte apoptosis. The effect of vitamin E on apoptosis regulation was weaker than the effects of erdosteine and NAC. Erdosteine, NAC and vitamin E significantly reduced the increases in the local production of TNF-alpha and heart MPO activity. This findings suggest that the effects of erdosteine and NAC on apoptosis regulation are stronger than that of vitamin E.     

The ameliorating effects of vitamin E on hepatic antioxidant system and xenobiotic-metabolizing enzymes in fenvalerate-exposed iodine-deficient rats

This study investigated the effects of vitamin E (VE) on hepatic antioxidant system and drug-metabolizing enzymes in fenvalerate (FEN)-exposed iodine-deficient (ID) Wistar rats. ID was produced by perchlorate containing drinking water. VE was introduced by a loading dose of 100?mg/kg/d, i.g. for the first three days in the last week of feeding period; then with a single maintenance dose of 40?mg/kg on the 4th day. During last week, FEN groups (F) received 100?mg/kg/d, i.p. FEN. VE alone did not significantly affect thyroid hormones and antioxidant parameters; however, significantly increased total cytochrome P450 (38%) and cytochrome b5 levels (36%). In all ID groups, plasma thyroid-stimulating hormone (TSH) levels increased markedly, but remained at control level in vitamin E plus FEN receiving iodine-deficient group (IDVF) group. Glutathione peroxidase activity showed marked increases in F (19%) and FEN-exposed iodine-deficient group (IDF, 48%) groups. FEN treatment significantly increased total cytochrome P450 (28%) and thiobarbituric acid reactive substance levels (36%), as well as 7-ethoxyresorufin O-deethylase (120%), 7-penthoxyresorufin O-deethylase (139%) and glutathione S-transferase (15%) activities and decreased total glutathione concentrations (28%) versus control. Overall results suggest that vitamin E has ameliorating effects on the measured parameters in ID and/or FEN exposure.     

In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats

Reactive oxygen species (ROS) may be involved in the toxicity of chlorpyrifos-ethyl (CE) [O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphorothioate]. We have, therefore, examined the in vivo effects of CE on the rat erythrocyte antioxidant system and evaluated the ameliorating effects of melatonin and a combination of vitamin E and vitamin C on the oxidative damage induced by CE. The experimental groups were: (1) control group, (2) CE-treated group (CE), (3) vitamin E plus vitamin C treatment group (Vit), (4) melatonin-treated group (Mel), (5) vitamin E plus vitamin C plus CE treatment group (Vit + CE), and (6) melatonin plus CE treatment group (Mel + CE). Vitamin E and vitamin C were administered intramuscularly once a day for 6 consecutive days at 150 and 200 mg/kg, respectively, in the Vit and Vit + CE groups. Melatonin was administered intramuscularly at 10 mg/kg per day for 6 consecutive days in the Mel and Mel + CE groups. At the end of the fifth day, the rats of CE, Vit + CE and Mel + CE groups were treated orally with the first of two equal doses of 41 mg/kg CE, the second oral dose being given 21 h later. Blood samples were taken 24 h after the first CE administration. Levels of thiobarbituric acid reactive substance (TBARS), antioxidant defence potential (AOP), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were determined in erythrocytes. In comparison with the control group, oral administration of CE significantly (P < 0.05) stimulated TBARS activity while significantly (P < 0.05) inhibiting AOP and the activities of SOD and CAT. However, GSH-Px activity remained unchanged by CE treatment. Treatment with melatonin and vitamins E plus C significantly (P < 0.05) reduced the CE-induced increase of TBARS, and overcame the inhibitory effect of CE on SOD and CAT, but not on AOP. Melatonin treatment significantly (P < 0.05) increased only GSH-Px activity, irrespective of the effect of CE. These results suggest that CE treatment increases in vivo lipid peroxidation and decreases antioxidant defence by increasing oxidative stress in erythrocytes of rats, and melatonin and a combination of vitamin E and vitamin C can reduce this lipoperoxidative effect.     

Protective effects of cysteine, methionine and vitamin C on the stomach in chronically alcohol treated rats

A chronic intake of high dose alcohol may cause oxidative stress and inflammation in the stomach. It is hypothesized that cysteine-methionine and vitamin C may neutralize harmful compounds while potentiating the antioxidant capacity of the cell or tissue. The experimental animals were fed regular diets and were maintained for 90 days in the control group, the alcoholic group, which was given 2.5 g of 50% ethanol kg(-1) body wt. administered intragastrically every other day, or the alcoholic with antioxidant supplement group, to whom 2.5 g of 50% ethanol kg(-1) body wt. + a solution that contained 200 mg vitamin C, 100 mg cysteine and 100 mg methionine was administered intragastrically every other day. After the treatments, the stomach was taken for pathological and biochemical analysis. The stomach of the alcoholic group rats had higher scores of pathological findings compared with the control group, whereas the scores of the antioxidant-supplemented group were lower than the alcoholic group. In addition, the oxidized protein and lipid content in the stomachs of the alcoholic group were significantly higher than the control, but antioxidant supplementation lowered the amount of oxidation in the antioxidant supplemented group. The amount of stomach glutathione in the alcoholic group was higher than that of the control and antioxidant-supplemented groups. Interestingly, the level of total thiol in the stomach tissue of rats with antioxidant supplement was statistically higher than that of the control and alcoholic groups. In conclusion, the scores of the pathological findings in the stomach of rats with the antioxidant supplement were lower than the chronic alcohol-treated rats, albeit the amount of total thiol was increased in this group. Moreover, chronic alcohol treatment led to an increase in the level of lipid and protein oxidation in the stomach tissue of rats. A simultaneous intake of ascorbate/l-cys/l-met along with ethanol attenuated the amount of oxidation which suggested that cysteine-methionine and vitamin C could play a protective role in the stomach against oxidative damage resulting from chronic alcohol ingestion.     

A comparative study of antioxidants S-allyl cysteine sulfoxide and vitamin E on the damages induced by nicotine in rats

The dietary consumption of antioxidant-rich fruits and vegetables is inversely correlated with the incidence of various diseases like cardiovascular diseases and lung cancer. We have tried to find out how far the S-allyl cysteine sulfoxide (SACS) isolated from garlic (Allium Sativum L.) can combat the nicotine-induced peroxidative damage in rats. The effects have been compared with the standard antioxidant vitamin E. Administration of SACS or vitamin E (100 mg/kg) to nicotine (0.6 mg/kg) treated rats for 21 days showed decreased concentrations of thiobarbituric acid reactive substances, hydroperoxides, and conjugated dienes in liver, lungs, and heart as compared with the values found in rats treated with nicotine alone. The activities of catalase and superoxide dismutase increased. The levels of the antioxidants like vitamins A, C, and E in the liver and glutathione in all tissues increased significantly in SACS-treated or vitamin E fed rats. However, the antioxidant status was higher when vitamin E was administered as compared with SACS administered to nicotine-treated rats.     

The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of pulmonary cells

This study was conducted to investigate the frequency of apoptosis in the pulmonary epithelial cells of rats after intratraperitoneal nicotine injection, in order to examine the role of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-alpha)] in nicotine-induced lung damage, and to determine the protective effects of three known antioxidant agents [N-acetylcysteine (NAC), erdosteine, and vitamin E] on the lung toxicity of nicotine in the lungs. Female Wistar rats were divided into seven groups, each composed of nine rats: two negative control groups, two positive control groups, one erdosteine-treated group (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group (500 mg/kg). Nicotine was injected intraperitoneally at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally, treatment was continued until the rats were killed. Lung tissue samples were stained with hematoxylin-eosin (H&E) for histopathological assessments. The apoptosis level in the lung bronchiolar and alveolar epithelium was determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. Cytoplasmic TNF-alpha in the bronchiolar and alveolar epithelial cells and the lung MPO activity were evaluated immunohistochemically. The protective effect of vitamin E on lung histology was stronger than that of erdosteine or NAC. Treatment with erdosteine, NAC, and vitamin E significantly reduced the rate of nicotine-induced pulmonary epithelial cell apoptosis, and there were no significant differences in apoptosis among the three antioxidants groups. Erdosteine, NAC, and vitamin E significantly reduced the increases in TNF-alpha staining and lung MPO activity. The effects of erdosteine on the increases in the local TNF-alpha level and lung MPO activity were weaker than that of NAC or vitamin E. This findings suggest that erdosteine and NAC can be as effective as vitamin E in protecting against nicotine-induced pulmonary cell apoptosis.     

Regulation of nicotine-induced apoptosis of pulmonary artery endothelial cells by treatment of N-acetylcysteine and vitamin E

This study investigated the frequency of apoptosis in rat pulmonary artery endothelial cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO), tumour necrosis factor alpha (TNF-alpha), and vascular endothelial growth factor (VEGF) in nicotine-induced vascular damage and the protective effects of two known antioxidant agents, N-acetylcysteine (NAC) and vitamin E. Female Wistar rats were divided into four groups, each composed of nine rats: negative control group, positive control group, NAC-treated group (500 mg/kg), and vitamin E-treated group (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Lung tissue samples were stained with hematoxylin-eosin (H&E) for histopathological assessments. Apoptosis level in endothelial cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling) method. Staining of cytoplasmic TNF-alpha and VEGF in endothelial cells, and perivascular MPO activity were evaluated by immunohistochemistry. The treatments with NAC and vitamin E significantly reduced the rate of nicotine-induced endothelial cell apoptosis. NAC and vitamin E significantly reduced the increases in the local production of TNF-alpha and VEGF, and perivascular MPO activity. This findings suggest that NAC can be as effective as vitamin E in protecting against nicotine-induced endothelial cell apoptosis.     

Effects of vitamin E on reactive oxygen species-mediated 2,3,7,8-tetrachlorodi-benzo-p-dioxin toxicity in rat testis

This study was undertaken to investigate whether treatment with vitamin E protects rat testis from oxidative stress induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Male rats of Wistar strain were administered TCDD at doses of 1, 10 and 100 ng kg(-1) body wt. day(-1) for 45 days. Other groups of animals were co-administered TCDD (1, 10 and 100 ng kg(-1) body wt. day(-1)) and vitamin E (20 mg kg(-1) body wt. day(-1)) for 45 days. Animals administered TCDD and those co-administered TCDD and vitamin E did not show any significant change in body weight. Administration of TCDD decreased the weights of the testis, epididymis, seminal vesicles and ventral prostate. The daily sperm production decreased in the animals administered TCDD from the control values of 22.19 +/- 2.67 to 13.10 +/- 3.16 x 10(6). There was a significant decline in the activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase with concomitant increased levels of hydrogen peroxide and lipid peroxidation. Co-administration of TCDD and vitamin E did not show any significant changes in the weights of the testis, epididymis, seminal vesicles and ventral prostate. The daily sperm production remained unchanged in the animals co-administered TCDD and vitamin E. The activities of antioxidant enzymes and the levels of hydrogen peroxide and lipid peroxidation did not change in the animals co-administered TCDD and vitamin E. The results suggested that administration of TCDD induces oxidative stress in testis, and vitamin E could impart a protective effect against TCDD-induced oxidative stress.     

Oxidative stress induced by atrazine in rat erythrocytes: Mitigating effect of vitamin E

The present study investigates the propensity of atrazine to induce oxidative stress and its possible attenuation by vitamin E in rat erythrocytes, which is a convenient model to understand the oxidative damage induced by various xenobiotics. Experimental animals were administered atrazine (300?mg/kg body weight, daily) and/or vitamin E (100?mg/kg body weight, daily) orally for a period of 7, 14, and 21 days. Results indicated that the reduced glutathione (GSH) content of the erythrocytes of atrazine treated rats was significantly decreased as compared to the control group. Co-administration of vitamin E along with atrazine restored the GSH content of erythrocytes nearly to control levels. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione-s-transferase were found to be increased significantly in the erythrocytes accompanied by a decrease in the activity of the glucose-6-phosophate dehydrogenase, following atrazine exposure. On the other hand, when vitamin E was co-administered along with atrazine, activities of these enzymes were found to be restored significantly. In conclusion, results of the study demonstrated that atrazine induced oxidative stress in rat erythrocytes, in terms of increased activities of the various antioxidant enzymes, and decreased content of reduced glutathione. However, vitamin E administration ameliorated the effects of atrazine, suggesting that vitamin E is a potential antioxidant against atrazine-induced oxidative stress.     

N-acetylcysteine or trolox derivative mitigate the toxic effects of methanol on the antioxidant system of rat brain

The effect of two compounds: N-acetylcysteine (NAC) and trolox derivative (U-83836E) on the methanol induced impairment of the antioxidant system of the rat brain was studied in male Wistar rats (approx. 250 g body weight). The animals were divided into six main groups: control group (0.5 ml of physiological saline intragastrically), NAC group (150 mg/kg intraperitoneally-i.p), U-83836E group (10 mg/kg i.p.), methanol group (3 g/kg intragastrically), NAC+methanol and U-83836E+methanol groups. In these particular groups the changes in antioxidant parameters were observed for 6,12,24,48 h and 5 and 7 days. The results proved that the use of methanol and N-acetylcysteine increased the activities of Cu,Zn-superoxide dismutase, glutathione peroxidase and glutathione reductase by about 15,15 and 41%, respectively, in comparison to the group of rats receiving methanol alone. Similarly, the level of GSH increased by about 17%, the concentration of ascorbate by 20%, while the thiobarbituric acid-reactive substances (TBA-rs) diminished to the values as in control group. The use of new antioxidant U8383E and methanol showed less beneficial effect in the measured parameters however, it serves as a better protector for the methanol induced decrease in GSH-content. These data suggest that NAC and U-83836E mitigate the toxic effects of methanol on the antioxidant system of the rat brain.     

Zingiber officinale Roscoe alone and in combination with alpha-tocopherol protect the kidney against cisplatin-induced acute renal failure.

Oxidative stress due to abnormal production of reactive oxygen molecules (ROM) is believed to be involved in the etiology of toxicities of many xenobiotics. Evidences suggested that ROM is involved in the nephrotoxicity of a widely used synthetic anticancer drug cisplatin. The nephroprotective effects of ethanol extract of Zingiber officinale alone and in combination with vitamin E (alpha-tocopherol) were evaluated using cisplatin (single dose of 10 mg/kg body wt, i.p) induced acute renal damage in mice. The results of the study indicated that Z. officinale significantly and dose dependently protected the nephrotoxicity induced by cisplatin. The serum urea and creatinine levels in the cisplatin alone treated group were significantly elevated (P<0.01) with respect to normal group of animals. The levels were reduced in the Z. officinale (250 and 500 mg/kg, p.o) plus cisplatin, vitamin E (250 mg/kg) plus cisplatin, and Z. officinale (250 mg/kg) with vitamin E plus vitamin E treated groups. The renal antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and level of reduced glutathione (GSH) were declined; level of malondialdehyde (MDA) was elevated in the cisplatin alone treated group. The activities of SOD, CAT GPx and level of GSH were elevated and level of MDA declined significantly (P<0.05) in the Z. officinale (250 and 500 mg/kg) plus cisplatin and Z. officinale (250 mg/kg) with vitamin E plus cisplatin treated groups. The protective effect of Z. officinale (250 mg/kg body wt) was found to be better than that of vitamin E (250 mg/kg body wt). The results also demonstrated that combination of Z. officinale (250 mg/kg) with vitamin E (250 mg/kg) showed a better protection compared to their 250 mg/kg alone treated groups. This study concluded that ethanol extract of Z. officinale alone and in combination with vitamin E partially ameliorated cisplatin-induced nephrotoxicity. This protection is mediated either by preventing the cisplatin-induced decline of renal antioxidant defense system or by their direct free radical scavenging activity.     

Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens tissues in rats

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer but its clinical use is associated with nephrotoxicity. Several studies suggest that supplementation with antioxidant can influence cisplatin induced nephrotoxicity. In the present study, we investigated the effect of selenium with high dose vitamin E administration on lipid peroxidation (MDA) and scavenging enzyme activity in kidneys, liver and lens of cisplatin-induced toxicity in rats. Forty female Wistar rats were used. They were randomly divided into five groups. The first and second groups were used as control and cisplatin (6 mg/kg BW) intraperitoneally administrated groups. Groups III, IV and V received intraperitoneally five doses of selenium (1.5 mg/kg BW) and a high dose of vitamin E (1000 mg/kg BW) combination before, simultaneously and after with cisplatin, respectively. Glutathione peroxidase (GSH-Px), vitamin E and beta-carotene levels in the kidney, lens and liver, vitamin A and reduced glutathione (GSH) levels in the kidney were significantly (P<0.05 to <0.001) lower in the cisplatin group than in the control whereas there was a significant increase in kidney, liver and lens MDA levels in rats treated with cisplatin. The decreased antioxidant enzymes and vitamins and increased MDA levels in the kidney, lens and liver of animals administered with cisplatin were significantly (P<0.05 to <0.001) improved with selenium and a high dose vitamin E injection. In conclusion, this data demonstrates that there is an increase in lipid peroxidation in the kidney, liver and lens of animals administered with cisplatin whereas there is a decrease in antioxidant vitamins and enzymes. However, intraperitoneally injected selenium combined with a high dose of vitamin E seem to produce a significant improvement on antioxidants concentrations in rats treated before, simultaneously and after with cisplatin. The selenium with high dose vitamin E injection may play a role in preventing cisplatin-induced nephropathy and cataract formation in cancer patient.     

Endosulfan-induced cardiotoxicity and free radical metabolism in rats: the protective effect of vitamin E

Endosulfan is widely used in insect control and it is absorbed by both humans and animals through ingestion, inhalation and percutaneously. The aim of this work was to study antioxidant enzyme system which include superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and malondialdehyde (MDA), the end product of lipid peroxidation and ultrastructural changes that might occur in the heart tissue of adult male Wistar rats as a result of endosulfan intoxication. Vitamin E (200 mg/kg, twice a week), endosulfan (2 mg/kg, per day, once a day in corn oil) and vitamin E (200 mg/kg, twice a week)+endosulfan (2 mg/kg, per day, once a day in corn oil) combination were given to rats (n = 10/group) orally via gavage for 6 weeks. SOD, GPx, CAT activities and MDA level increased in the endosulfan-treated group heart tissue compared to control group (P < 0.01, P < 0.01, P < 0.05 and P < 0.01, respectively). SOD, GPx activities and MDA level decreased in the vitamin E + endosulfan-treated group compared to endosulfan-treated group (P < 0.05, P < 0.05 and P < 0.05, respectively). Decrease of CAT activity was not significant statistically in the vitamin E + endosulfan-treated group compared to endosulfan-treated group. CAT activity increased in the vitamin E + endosulfan treated group compared to control group (P < 0.05). Increase of SOD, GPx activities and MDA levels were not significant statistically in the vitamin E + endosulfan-treated group compared to control group. In electron microscopic investigations while cytoplasmic edema and swelling and vacuolization of mitochondria of myocardial cells in endosulfan-treated group was observing, only a weak swelling of mitochondria of myocardial cells in vitamin E + endosulfan-treated group was observed. We conclude that vitamin E significantly reduce endosulfan-induced cardiotoxicity in rats.     

Effect of beta-carotene supplementation on rats submitted to chronic ethanol ingestion

Chronic alcohol consumption is directly related to the induction of liver damage. The continuous use of ethanol induces the isoenzyme cytochrome P450CYP2E1, which promotes the formation of free radicals, resulting in lipid peroxidation. Among the main antioxidants are vitamin E, reduced glutathione (GSH), vitamin C, and beta-carotene. beta-Carotene has antioxidant activity per se, with a probable protective effect against different types of cancer. However, some studies have shown an increased number of cancer cells when beta-carotene is administered in the presence of chronic ethanol ingestion. On this basis, the objective of the present study was to assess the effect of beta-carotene supplementation on rats chronically treated with a hydroalcoholic solution by determining the levels of vitamin E, beta-carotene, GSH, and thiobarbituric acid reactive species (TBARS). Both the plasma and liver concentrations of beta-carotene were higher in the supplemented groups. Plasma vitamin E levels were decreased in the control group and liver vitamin E levels were significantly decreased (p < 0.05) in all groups compared to basal levels. GSH levels were increased over basal values in the group supplemented with beta-carotene for 14 days. TBARS values were increased as much as four-fold in the control group at 14 days, and declined again at 28 days, whereas they were increased in the supplemented group, with the increase remaining until the end of the experiment. The study indicates that beta-carotene had no beneficial effect as an antioxidant on rats submitted to chronic alcohol intake, and could be act as prooxidant when administered with ethanol.