Sesamin Protects against APAP-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Inflammatory Response via Deactivation of HMGB1/TLR4/NFκB Signal in Mice

作者全名："Du, Hui; Tong, Shiwen; Kuang, Ge; Gong, Xia; Jiang, Ningman; Yang, Xian; Liu, Hao; Li, Nana; Xie, Yao; Xiang, Yang; Guo, Jiashi; Li, Zhenhan; Yuan, Yinglin; Wu, Shengwang; Wan, Jingyuan"

作者地址："[Du, Hui; Kuang, Ge; Jiang, Ningman; Yang, Xian; Liu, Hao; Li, Nana; Xie, Yao; Xiang, Yang; Guo, Jiashi; Wan, Jingyuan] Chongqing Med Univ, Dept Pharmacol, Chongqing, Peoples R China; [Tong, Shiwen] Chongqing Med Univ, Affiliated Hosp 2, Dept Clin Nutr, Chongqing 400016, Peoples R China; [Gong, Xia] Chongqing Med Univ, Dept Anat, Chongqing, Peoples R China; [Li, Zhenhan] Chongqing Tradit Chinese Med Hosp, Chongqing, Peoples R China; [Yuan, Yinglin] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Clin Immunol Translat Med Key Lab Sichuan Prov, Chengdu, Peoples R China; [Wu, Shengwang] Army Med Univ, Xinqiao Hosp, Dept Hematol, Chongqing, Peoples R China"

通信作者："Wan, JY (通讯作者)，Chongqing Med Univ, Dept Pharmacol, Chongqing, Peoples R China."

来源：JOURNAL OF IMMUNOLOGY RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001060504200001

JCR分区：Q2

影响因子：3.5

年份：2023

卷号：2023

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Acetaminophen (APAP) overdose would lead to liver toxicity and even acute liver failure in severe cases by triggering an inflammatory response and oxidative stress. Sesamin has been reported to possess anti-inflammatory and antioxidant actions in several animal disease models. In the present study, the effects and mechanisms of sesamin on APAP-induced acute liver injury (ALI) were explored. The results showed that pretreatment with sesamin significantly alleviated APAP-induced ALI, as indicated by decreased serum aminotransferase activities, hepatic pathological damages, and hepatic cellular apoptosis. But sesamin has no significant effects on the expression of cytochrome P450 2E1 (CYP2E1), APAP-cysteine adducts (APAP-CYS) production, and glutathione content in the liver of APAP-administered mice. Moreover, APAP-induced liver oxidative stress and inflammatory response also were remarkedly attenuated by sesamin, including reducing hepatic reactive oxygen species levels, promoting antioxidant generation, and inhibiting the expression of TNF-alpha and IL-1 ss, as well as decreasing inflammatory cell recruitment. Notably, sesamin inhibited serum high-mobility group box 1 (HMGB1) releases and blocked hepatic activation of Toll-like receptor 4 (TLR4)-interleukin 1 receptor-associated kinase 3-nuclear factor kappa B (NF-kappa B) signaling pathway in APAPadministered mice. These findings indicated that sesamin could mitigate APAP-induced ALI through suppression of oxidative stress and inflammatory response, which might be mediated by the deactivation of HMGB1/TLR4/NF-kappa B signaling in mice."

基金机构："Natural Science Foundation of Chongqing, China [cstc2019jcyj-msxmX0863]; Program for Outstanding Young Talent of Chongqing Kuanren Hospital"

基金资助正文："We are grateful to Rong Jiang for her methodology assistance in liver tissue slicing. This study was funded by the Natural Science Foundation of Chongqing, China (cstc2019jcyj-msxmX0863) and the Program for Outstanding Young Talent of Chongqing Kuanren Hospital."