Hydrogen sulfide protects against acetaminophen-induced acute liver injury by inhibiting apoptosis via the JNK/MAPK signaling pathway |
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Authors: | Xiaoyong Li Jiaqiong Lin Yan Lin Zena Huang Yuguo Pan Peng Cui Chicai Yu Cun Cai Jintang Xia |
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Institution: | 1. Department of General Surgery, The Third Affiliated hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China;2. Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China;3. Department of Nephrology, The Third Affiliated hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China;4. Department of Critical Care Medicine and Emergency, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China |
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Abstract: | Acetaminophen (APAP) is a widely used over-the-counter analgesic and antipyretic. It can cause hepatotoxicity. Recent studies demonstrated that hydrogen sulfide (H2S) exhibits cell protection in several cell types. This study was designed to investigate whether H 2S ameliorated APAP-induced acute liver injury and to elucidate its mechanisms. In this study, we analyzed the detailed biological and molecular processes of APAP-induced hepatotoxicity using a bioinformatics analysis, which showed that apoptosis and the c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase pathway were confirmed to play critical roles in these processes. We further investigated the protective effects of H 2S on APAP-induced hepatotoxicity. In vivo, we observed that the exogenous supplement of H 2S ameliorated APAP-induced liver injury. Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) systems were the endogenous pathway of H 2S. The expression of CBS/CSE was decreased in APAP-treated mice, while H 2S could significantly restore it. In addition, APAP-induced JNK activation was inhibited by H 2S in vivo. In vitro, H 2S abolished the active effects of APAP on caspase3, Bax, and Bcl-2 expressions as well as JNK phosphorylation in hepatocytes. It was found through flow cytometry that the amount of APAP-induced apoptotic hepatocytes was decreased in the presence of H 2S. In conclusion, our results suggested that H 2S attenuated APAP-induced apoptosis in hepatocytes through JNK/MAPK siganaling pathway. |
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Keywords: | acetaminophen (APAP) apoptosis hepatotoxicity hydrogen sulfide (H2S) c-Jun N-terminal kinase/mitogen-activated protein kinase (JNK/MAPK) |
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