Toxicity assessment of hydrogen peroxide on Toll-like receptor system, apoptosis, and mitochondrial respiration in piglets and IPEC-J2 cells

// Jie Yin 1, 2, * , Miaomiao Wu 1, * , Yuying Li 1, 2, * , Wenkai Ren 1, 2 , Hao Xiao 1 , Shuai Chen 1, 2 , Chunyong Li 1 , Bie Tan 1 , Hengjia Ni 1 , Xia Xiong 1 , Yuzhe Zhang 1 , Xingguo Huang 3, 4 , Rejun Fang 3 , Tiejun Li 1, 4 , Yulong Yin 1, 4, 5 1 Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China 2 University of Chinese Academy of Sciences, Beijing 100039, China 3 Department of Animal Science, Hunan Agriculture University, Changsha, Hunan 410125, China 4 Hunan Co-Innovation Center of Animal Production Safety, Changsha, Hunan 410128, China 5 College of Animal Science of South China Agricultural University, Guangzhou 510642, China * These authors contributed equally to this work Correspondence to: Tiejun Li, email: tjli@isa.ac.cn Yulong Yin, email: yinyulong@isa.ac.cn Keywords: H 2 O 2 , TLRs, apoptosis, mitochondrial respiration, piglet Received: September 28, 2016 Accepted: November 24, 2016 Published: December 09, 2016 ABSTRACT In this study, expressions of toll-like receptors (TLRs) and apoptosis-related genes in piglets and mitochondrial respiration in intestinal porcine epithelial cells were investigated after hydrogen peroxide (H 2 O 2 ) exposure. The in vivo results showed that H 2 O 2 influenced intestinal expressions of TLRs and apoptosis related genes. H 2 O 2 treatment (5% and 10%) downregulated uncoupling protein 2 (UCP2) expression in the duodenum ( P < 0.05), while low dosage of H2O2 significantly increased UCP2 expression in the jejunum ( P < 0.05). In IPEC-J2 cells, H 2 O 2 inhibited cell proliferation ( P < 0.05) and caused mitochondrial dysfunction via reducing maximal respiration, spare respiratory, non-mitochondrial respiratory, and ATP production ( P < 0.05). However, 50 uM H 2 O 2 significantly enhanced mitochondrial proton leak ( P < 0.05). In conclusion, H 2 O 2 affected intestinal TLRs system, apoptosis related genes, and mitochondrial dysfunction in vivo and in vitro models. Meanwhile, low dosage of H 2 O 2 might exhibit a feedback regulatory mechanism against oxidative injury via increasing UCP2 expression and mitochondrial proton leak.