Roles of oxidative stress/JNK/ERK signals in paraquat-triggered hepatic apoptosis

• DOI: 10.1016/j.crtox.2024.100155
• Publication Date: 2024-02-10T16:54:35Z
• Authors: Kuan-I Lee; Kai-Min Fang; Chun-Ying Kuo; Chun-Fa Huang; Shing-Hwa Liu; Jui-Ming Liu; Wei-Cheng Lai; Kai-Chih Chang; Chin-Chuan Su; Ya-Wen Chen
• Keywords: Paraquat; 0301 basic medicine; 03 medical and health sciences; ERK1/2; Oxidative stress; RA1190-1270; Hepatotoxicity; Toxicology. Poisons; Apoptosis; JNK; Articles from the special issue on Invite 2023 edited by Thomas Knudsen

Paraquat (PQ), a toxic and nonselective bipyridyl herbicide, is one of the most extensively used pesticides in agricultural countries. In addition to pneumotoxicity, liver an important target organ for PQ poisoning humans. However, mechanism hepatotoxicity remains unclear. this study, we found that exposure rat hepatic H4IIE cells (0.1–2 mM) induced significant cytotoxicity apoptosis, which was accompanied by mitochondria-dependent apoptotic signals, including loss mitochondrial membrane potential (MMP), cytosolic cytochrome c release, changes Bcl-2/Bax mRNA ratio. Moreover, (0.5 markedly JNK ERK1/2 activation, but not p38-MAPK. Blockade signaling pretreatment with specific pharmacological inhibitors SP600125 PD98059, respectively, effectively prevented PQ-induced cytotoxicity, dysfunction, events. Additionally, stimulated oxidative stress-related reactive oxygen species (ROS) generation intracellular glutathione (GSH) depletion, could be reversed antioxidant N-Acetylcysteine (NAC). Buffering stress response NAC also abrogated hepatotoxicity, MMP loss, phosphorylation protein, however, or ERK did suppress ROS PQ-treated cells. Collectively, these results demonstrate induces cell toxicity death via stress-dependent JNK/ERK activation-mediated downstream mitochondria-regulated pathway.