Effects of carbon tetrachloride on oxidative stress, inflammatory response and hepatocyte apoptosis in common carp (Cyprinus carpio).
In the present study, the cellular and molecular mechanism of carbon tetrachloride (CCl4)-induced hepatotoxicity in fish was investigated by studying the effects of CCl4 on the oxidative stress, inflammatory response and hepatocyte apoptosis. Common carp were given an intraperitoneal injection of 30% CCl4 in arachis oil (0.5ml/kg body weight). At 72h post-injection, blood were collected to measure glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase (GOT), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione (GSH), total antioxidant capacity (T-AOC) and malondialdehyde (MDA), liver samples were taken to analyze toll-like receptor 4 (TLR4), cytochrome P450 2E1 (CYP2E1) and gene expressions of inflammatory cytokines and nuclear factor-κB (NF-κB/cREL). Cell viability and apoptosis were analyzed after treatment of the primary hepatocytes with CCl4 at 8mM. The results showed that CCl4 significantly increased the levels of GPT, GOT, MDA, TLR4 and CYP2E1, reduced the levels of SOD, GPx, CAT, GSH and T-AOC, and up-regulated the gene expressions of NF-κB/cREL and inflammatory cytokines including tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), IL-1β, IL-6 and IL-12. In vitro, CCl4 caused a dramatic loss in cell viability and induced hepatocyte apoptosis. Overall results suggest that oxidative stress lipid peroxidation, and TNF-α/NF-κB and TRL4/NF-κB signaling pathways play important roles in CCl4-induced hepatotoxicity in fish.
Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
Rui
R
Jia
Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; International Joint Research Laboratory for Fish Immunopharmacology, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
Li-Ping
LP
Cao
Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; International Joint Research Laboratory for Fish Immunopharmacology, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
Jin-Liang
JL
Du
Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China.
Jia-Hao
JH
Wang
Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China.
Ying-Juan
YJ
Liu
National Agricultural Research Center, Research Institute for Fisherie and, Aquaculture, Anna Light 8, Szarvas 5440, Hungary.
Galina
G
Jeney
Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China. Electronic address: xup@ffrc.cn.
Pao
P
Xu
Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; International Joint Research Laboratory for Fish Immunopharmacology, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China. Electronic address: yingj@ffrc.cn.
Guo-Jun
GJ
Yin
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002347:Carps; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D016207:Cytokines; D016328:NF-kappa B; D014874:Water Pollutants, Chemical; D002251:Carbon Tetrachloride; D010088:Oxidoreductases
Apoptosis; Carbon tetrachloride; Cyprinus carpio; Inflammatory cytokines; Nuclear translocation factor