Aflatoxin B1 invokes apoptosis via death receptor pathway in hepatocytes

// Muhammad Jameel Mughal 1 , Xi Peng 2 , Yi Zhou 3 , Jing Fang 1 1 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China 2 Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), College of Life Sciences, China West Normal University, Nanchong, Sichuan, China 3 Life Science Department, Sichuan Agricultural University, Yaan, Sichuan, PR China Correspondence to: Xi Peng, email: pengxi197313@163.com Jing Fang, email: fangjing4109@163.com Keywords: aflatoxin B1, apoptosis, carcinogenicity, oxidative stress, hepatotoxicity Received: September 30, 2016 Accepted: November 24, 2016 Published: December 24, 2016 ABSTRACT The fungal metabolites produced by Aspergillus flavus and Aspergillus parasiticus cause detrimental health effects on humans and animals. Particularly aflatoxin B 1 (AFB 1 ) is the most studied and a well-known global carcinogen, producing hepatotoxic, genotoxic and immunotoxic effects in multiple species. AFB 1 is shown to provoke liver dysfunctioning by causing hepatocytes apoptosis and disturbing cellular enzymatic activities. In liver, AFB 1 causes apoptosis via extrinsic mechanism because of high expression of death receptor pathway. The detailed mechanism of AFB 1 induced hepatocytes apoptosis, via death receptor pathway still remains elusive. So the present study was conducted to explore apoptotic mechanism initiated by death receptors and associated genes in aflatoxin B1 induced liver apoptosis in chickens fed with AFB 1 for 3 weeks. Results from the present study displayed histopathological and ultrastructural changes in liver such as hydropic degeneration, fatty vacuolar degeneration and proliferation of bile duct in hepatocytes in AFB 1 group, along with imbalance between reactive oxygen species (ROS) and antioxidant defense system upon AFB 1 ingestion. Moreover, AFB 1 intoxicated chickens showed upregulation of death receptors FAS, TNFR1 and associated genes and downregulation of inhibitory apoptotic proteins XIAP and BCL-2. The results obtained from this novel and comprehensive study including histopathological, ultrastructural, flow cytometrical and death receptor pathway gene expression profiles, will facilitate better understanding of mechanisms and involvement of death receptor pathway in hepatocytes apoptosis induced by AFB 1 and ultimately may be helpful in bringing down the toxigenic potential of AFB 1 .