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This study was planned to investigate the protective effect of l(+)-ascorbic acid (Vit C) on CCl4-induced hepatotoxicity and oxidative stress in the liver of Wistar rats (Rattus Norvegicus, strain Wistar). Twenty-four adult male Wistar rats were fed with standard rat chow diet for 10 days and randomly were divided into four groups of six each as follows: (1) control, (2) CCl4, (3) 'CCl4 + Vit C', (4) Vit C groups. CCl4 was applied to rats belonging to CCl4 and 'CCl4 + Vit C' groups subcutaneously at 1 mg kg−1 dose CCl4 for 3 days. Vit C applied to 'CCl4 + Vit C' and 'Vit C' group rats intraperitoneally at 300 mg kg−1 dose for 3 days. All rats were sacrificed and livers were quickly removed on the fourth day of the experiment. MDA, total glutathione (T.GSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) activities were measured in the liver of all groups of rats and also serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were detected to determine liver functions in all groups of rats. Histopathological changes were evaluated by light and transmission electron microscopes. In 'CCl4 + Vit C' group, MDA level was significantly decreased ( p < 0.05) and SOD, CAT, GSH-PX activities were significantly increased ( p < 0.005, 0.01, 0.05) respectively, T.GSH level was significantly increased ( p < 0.005) and serum ALT and AST activities were significantly decreased ( p < 0.01, 0.05), respectively, when compared with CCl4 group. These results show that Vit C has a highly protective effect on hepatotoxicity and oxidative stress caused by CCl4. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The aims of this study were to observe the changes in antioxidative defense enzymes and renal morphology after 7,12-dimethyl-benz[ a]anthracene (7,12-DMBA) administration in mice and to investigate the possible protective effects of melatonin against 7,12-DMBA-induced renal damage in comparison with vitamin E + selenium (vit E + Se). Forty female mice were divided into four groups: control, DMBA, DMBA + vit E + Se and DMBA + melatonin. In the DMBA group, mice were given injections of 7,12-DMBA (20 mg/kg). DMBA + vit E + Se group mice received injections of 7,12-DMBA + vit E + Se (20 mg/kg + 90 mg/kg + 1.8 μg/kg). In the melatonin group, mice were given injections of 7,12-DMBA + melatonin (20 mg/kg + 4.2 mg/kg). The experiment lasted for 21 days. Mice were killed and the kidneys were taken for enzyme analyses and histologic examination. Catalase (CAT) and glutathione peroxidase (GSH-Px) activities were found significantly decreased in the DMBA group and in the DMBA + vit E + Se group when compared with the control group ( P < 0.05), whereas CAT and GSH-Px activities were found significantly elevated in the DMBA + melatonin group when compared with the control ( P < 0.05) and the DMBA group ( P < 0.01). Exposure to DMBA resulted in tubular alterations in renal cortex. Morphometric analysis revealed proximal and distal tubular damage ( P < 0.05). These alterations were found to be prevented by melatonin but not with vit E + Se administration. These results reveal that melatonin stimulates CAT and GSH-Px activities and prevents renal injury better than vit E + Se combination in mice kidneys. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the beneficial effects of caffeic acid phenethyl ester (CAPE) on gentamicin (GM)-induced nephrotoxicity in Wistar rats. Twenty-one adult Wistar rats were divided into three groups as follows: control group, GM and GM + CAPE group. Control group rats were injected with 5% ethanol, GM group rats were treated with 100 mg/kg GM and GM + CAPE group were pretreated with 10 μmol/kg CAPE for 2 days, then exposed to GM at the same dose. Drug injections were applied for 12 days. Twenty-four hours after the last injection, rats were killed and kidneys were quicky removed. Tissue malondialdehyde (MDA) measurements and microscopic examination of kidneys were performed. In the GM group, significant increases in MDA levels were observed (P < 0.05). These changes were found to be normalized in the GM + CAPE group. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules were found to be prevented by CAPE pretreatment. In conclusion, CAPE exerted an improvement on GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation. [ABSTRACT FROM AUTHOR]

Doxorubicin (Dox) is a widely used antineoplastic drug. Oxygen radical-induced injury of membrane lipids is considered to be the most important factor responsible for the development of Dox-induced cardiotoxicity. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and its pharmacological concentrations have been shown to reduce Dox-induced cardiac damage. However, the physiological role of melatonin in the prevention of this damage is unknown. We investigated physiological and pharmacological effects of melatonin on Dox-induced changes in the levels of malondialdehyde (MDA), a lipid peroxidation product, and morphological changes in heart. Rats were pinealectomized (Px) or sham-operated (control) 2 months before the studies. Melatonin was administered [4 mg/kg, intraperitoneally (i.p.)] 1 hr before or 24 hr after the administration of a single dose of Dox (20 mg/kg, i.p.) and continued for 2 days. The levels of MDA Dox was found to be significantly higher in the Px rats (55.9 ± 0.6 nmol/g tissue) than intact control animals (42.6 ± 0.4). Dox administration to Px and non-Px rats significantly increased the MDA levels. Pre- and post-treatment with melatonin in both Px and intact rats significantly reduced MDA levels. Morphological changes parallelled the MDA alterations. These findings strongly suggest that both physiological and pharmacological concentrations of melatonin are important in protecting the heart from Dox-induced damage in rats. It would seem valuable to test melatonin in clinical trials for prevention of possible heart damage associated with Dox. [ABSTRACT FROM AUTHOR]