Nickel chloride-induced apoptosis via mitochondria- and Fas-mediated caspase-dependent pathways in broiler chickens

// Hongrui Guo 1 , Hengmin Cui 1, 2 , Jing Fang 1, 2 , Zhicai Zuo 1, 2 , Junliang Deng 1, 2 , Xun Wang 1, 2 , Ling Zhao 1, 2 , Bangyuan Wu 1 , Kejie Chen 1 , Jie Deng 1 1 College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya’an 625014, China Correspondence to: Hengmin Cui, email: cui580420@sicau.edu.cn Keywords: NiCl 2 , apoptosis, mitochondria-mediated caspase-dependent apoptosis, Fas-mediated caspase-dependent apoptosis, kidney Received: July 02, 2016 Accepted: October 13, 2016 Published: October 27, 2016 ABSTRACT Ni, a metal with industrial and commercial uses, poses a serious hazard to human and animal health. In the present study, we used flow cytometry, immunohistochemistry and qRT-PCR to investigate the mechanisms of NiCl 2 -induced apoptosis in kidney cells. After treating 280 broiler chickens with 0, 300, 600 or 900 mg/kg NiCl 2 for 42 days, we found that two caspase-dependent pathways were involved in the induced renal tubular cell apoptosis. In the mitochondria-mediated caspase-dependent apoptotic pathway, cyt-c, HtrA2/Omi, Smac/Diablo, apaf-1, PARP, and caspase-9, 3, 6 and 7 were all increased, while. XIAP transcription was decreased. Concurrently, in the Fas-mediated caspase-dependent apoptotic pathway, Fas, FasL, caspase-8, caspase-10 and Bid levels were all increased. These results indicate that dietary NiCl 2 at 300+ mg/kg induces renal tubular cell apoptosis in broiler chickens, involving both mitochondrial and Fas-mediated caspase-dependent apoptotic pathways. Our results provide novel insight into Ni and Ni-compound toxicology evaluated in vitro and in vivo .