Research Papers: Pathology:

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

Yue Zhang, Zhengkai Wei, Weijian Liu, Jingjing Wang, Xuexiu He, Hailong Huang, Jiali Zhang and Zhengtao Yang _

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Oncotarget. 2017; 8:3773-3780. https://doi.org/10.18632/oncotarget.13931

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Yue Zhang1, Zhengkai Wei2, Weijian Liu2, Jingjing Wang2,Xuexiu He2, Hailong Huang1, Jiali Zhang1 and Zhengtao Yang2

1 College of Animal Science and Technology, Jilin Agricultural University, Changchun, People’s Republic of China

2 Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People’s Republic of China

Correspondence to:

Zhengtao Yang, email:

Jiali Zhang, email:

Keywords: As2O3; melatonin; liver injury; Nrf-2; Pathology Section

Received: April 09, 2016 Accepted: October 29, 2016 Published: December 14, 2016


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.

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