The aim of this study was to investigate the protective effect of root extract of Withania somnifera (WS) against gamma-irradiation-induced oxidative stress and DNA damage in hepatic tissue after whole body gamma-irradiation. Fourty male albino rats were divided into four groups. In the control group, rats were administered vehicle by tube for 7 consecutive days. The second group were administered WS (100mg/kg, by gavage) for 7 consecutive days. Animals in the third group were administered vehicle by tube for 7 consecutive days, then exposed to single dose gamma-irradiation (6 Gy). The fourth group received WS for 7 consecutive days, one hour later rats were exposed to gamma-irradiation. Irradiation hepatotoxicity was manifested biochemically by an increase in hepatic serum enzymes, significant elevation in levels of malondialdehyde (MDA) and total nitrate/nitrite NO(x), significant increase in heme oxygenase activity (HO-1), as well as a significant decrease in reduced glutathione (GSH) content and the activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) in hepatic tissues. Marked DNA damage was observed. WS pretreatment showed significant decrease in serum hepatic enzymes, hepatic NO(x) and MDA levels and DNA damage, significant HO-1 induction and significant increase in SOD, GSHPx activities and GSH content compared to irradiated group. These observations suggest that WS could be developed as a potential preventive drug for ionizing irradiation induced hepatotoxicity disorders via enhancing the antioxidant activity and induction of HO-1.
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