期刊
FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.797499
关键词
hepatotoxicity. atractylenolide I; acetaminophen; liver injury; TLR4/MAPKs/NF-?B; inflammation
资金
- National Natural Science Foundation of China [81973041, 81773981, 82004353]
- Zhejiang Natural Science Foundations for Distinguished Young Scholars [LR20H260001]
- Zhejiang Natural Science Foundation [LQ20H290005]
- Zhejiang Medical and Health Science and Technology Plan [2019KY113]
- Zhejiang Traditional Chinese Medicine Science and Technology Plan [2019ZQ010]
This study aimed to evaluate the protective effects of Atractylenolide I (AO-I) against acetaminophen (APAP)-induced acute liver injury. The results showed that AO-I treatment significantly reversed APAP-induced liver injury, alleviated oxidative stress and inflammation, and inhibited the activation of TLR4/MAPKs/NF-kappa B pathways. AO-I is a potential therapeutic compound for APAP-induced hepatotoxicity.
Background: Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), induces hepatocyte necrosis, and leads to acute liver failure. Atractylenolide I (AO-I), a phytochemical found in Atractylodes macrocephala Koidz, is known to exhibit antioxidant activity. However, its clinical benefits against drug-induced liver injury remain largely unclear. Purpose: This study aimed at evaluating the protective effects of AO-I against APAP-induced acute liver injury. Methods: C57BL/6 mice were administered 500 mg/kg APAP to induce hepatotoxicity. AO-I (60 and 120 mg/kg) was intragastrically administered 2 h before APAP dosing. Liver histopathological changes, oxidative stress and hepatic inflammation markers from each group were observed. Results: We observed that AO-I treatment significantly reversed APAP-induced liver injury, as evidenced by improved plasma alanine transaminase (ALT) level, aspartate aminotransferase (AST) and liver H&E stain. APAP treatment increased liver malondialdehyde (MDA) content and reduced catalase (CAT) and glutathione (GSH) level; however, these effects were alleviated by AO-I intervention. Moreover, AO-I treatment significantly inhibited APAP-induced activation of pro-inflammatory factors, such as IL-1 beta, IL-6, and TNF-alpha, at both the mRNA and protein levels. Mechanistic studies revealed that AO-I attenuated APAP-induced activation of TLR4, NF-kappa B and MAPKs (including JNK and p38). Conclusion: AO-I mediates protective effects against APAP-induced hepatotoxicity via the TLR4/MAPKs/NF-kappa B pathways. Thus, AO-I is a candidate therapeutic compound for APAP-induced hepatotoxicity.
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