title: Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K/AKT pathway.
abstract: 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.
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Zhengkai
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Xuexiu
authors.initials: X
authors.lastname: He
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun, People's Republic of China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Huang
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun, People's Republic of China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000009:adverse effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D001152:Arsenicals; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010087:Oxides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D008550:Melatonin; D000077237:Arsenic Trioxide
keywords: As2O3; Nrf-2; Pathology Section; liver injury; melatonin