Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K/AKT pathway

Melatonin has been demonstrated to have anti-inflammatory and antioxidant effects. The aim of this study was to investigate the protective effects of melatonin on arsenic trioxide (As(2)O(3))-induced toxicity in liver and oxidative stress in rats. The rats were injected with 3mg/kg As(2)O(3) on alternate days and melatonin was given with an intraperitoneal injection (i.p.) 1 h before As(2)O(3) treatment. On the 8th days, the rats were killed to determine liver histological injury, antioxidant activities and accumulation of arsenic in liver tissues. Our results showed that melatonin attenuated As(2)O(3)-induced hepatic pathological damage, liver parameters, liver ROS level, MDA level, and the retention of arsenic in liver tissues. Melatonin also improved the antioxidant enzymes SOD, GPX, and CAT activity induced by As(2)O(3). Furthermore, melatonin improved the expression of Nrf2 and HO-1 In addition, melatonin was found to activate PI3K/AKT pathway. In conclusion, our results indicated that melatonin protected against As(2)O(3)-induced liver injury by inducing Nrf2/HO-1 expression via upregulation of PI3K/AKT pathway.