Zhang Yue, Wei Zhengkai, Liu Weijian, Wang Jingjing, He Xuexiu, Huang Hailong, Zhang Jiali, Yang Zhengtao
College of Animal Science and Technology, Jilin Agricultural University, Changchun, People's Republic of China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
Oncotarget. 2017 Jan 17;8(3):3773-3780. doi: 10.18632/oncotarget.13931.
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 (As2O3)-induced toxicity in liver and oxidative stress in rats. The rats were injected with 3mg/kg As2O3 on alternate days and melatonin was given with an intraperitoneal injection (i.p.) 1 h before As2O3 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 As2O3-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 As2O3. 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 As2O3-induced liver injury by inducing Nrf2/HO-1 expression via upregulation of PI3K/AKT pathway.
褪黑素已被证明具有抗炎和抗氧化作用。本研究的目的是探讨褪黑素对大鼠三氧化二砷（As2O3）诱导的肝脏毒性和氧化应激的保护作用。大鼠每隔一天注射3mg/kg As2O3，并在As2O3处理前1小时腹腔注射（i.p.）褪黑素。在第8天，处死大鼠以确定肝脏组织学损伤、抗氧化活性以及肝脏组织中砷的积累。我们的结果表明，褪黑素减轻了As2O3诱导的肝脏病理损伤、肝脏参数、肝脏ROS水平、MDA水平以及肝脏组织中砷的潴留。褪黑素还提高了As2O3诱导的抗氧化酶SOD、GPX和CAT的活性。此外，褪黑素改善了Nrf2和HO-1的表达。另外，发现褪黑素可激活PI3K/AKT通路。总之，我们的结果表明，褪黑素通过上调PI3K/AKT通路诱导Nrf2/HO-1表达，从而对As2O3诱导的肝损伤起到保护作用。
