Hepatoprotective effects of vitamin E/selenium against malathion-induced injuries on the antioxidant status and apoptosis-related gene expression in rats

抄録

The present study is undertaken to evaluate the protective effect of vitamin E (α-tocopherol) and selenium (Se) against malathion (MTN)-induced oxidative stress and hepatic injuries in experimental rats. Male rats were randomly divided into eight groups comprised of 10 rats each. The 1^st group served as a negative control (C_N), whereas the 2^nd was supplemented with a combination of α-tocopherol (100 mg kg^-1 body weight, b.w.)/Se (0.1 mg kg^-1 bw). The 3^rd, 4^th and 5^th groups were respectively administered with increasing doses of MTN equivalent to _1/50 LD₅₀ (M_1/50), _1/25 LD₅₀ (M_1/25) and _1/10 LD₅₀ (M_1/10), respectively. The 6^th, 7^th and 8^th groups were administered the same doses of MTN as in the 3^rd, 4^th and 5^th groups with a concomitant supplementation with α-tocopherol/Se. Subchronic exposure of rats to MTN for 45 days resulted in statistical dose-dependent decrease in acetylcholinestrase (AChE) activity, increase in oxidative stress marker lipid peroxidation (LPO) and reduction in reduced glutathione (GSH) level. Moreover, the levels of glutathione persoxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were significantly decline in response to MTN exposure in a dose-dependent fashion. Furthermore, histopathological studies of liver in the rats which received MTN exhibited, moderate to severe degenerative and necrotic changes in the hepatocytes. Notably, the administration of α-tocopherol/Se protected the liver of rats exposed to MTN as evidenced by the appearance of normal histological structures, significant attenuation of the decline in all antioxidant enzymes tested (i.e. GPx, SOD and CAT), significant recovery in the GSH level and statistical reduction in LPO, as compared to the experimental rat. The effect of α-tocopherol/Se supplementation on transcriptional activity of three key stress and apoptosis-related genes (i.e., Tp53, CASP3 and CASP9), in response to MTN exposure in rats, was investigated. Results revealed a significant concentration-dependent up-regulation in the level of expression for the three genes examined, in response to MTN exposure, compared with the control. Interestingly, the supplementation of MTN-treated rats with α-tocopherol/Se modulates the observed significant dose-dependent up-regulation in the level of expression for three selected genes, indicative of an interfering role in the signaling transduction process of MTN-mediated poisoning. Taken together, these data suggest that the administration of α-tocopherol/Se may partially protect against MTN-induced hepatic oxidative stress and injuries.