Cannabidiol protects the liver from α-Amanitin-induced apoptosis and oxidative stress through the regulation of Nrf2.

Autor: Wang H; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Yang G; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Zhang X; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Zhang H; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Liu Y; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Wang C; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Miao L; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Li Y; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Huang Y; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China., Teng H; Department of Pathogen Biology and Immunology, School of Basic Medical Science, Kunming Medical University, Kunming, China., Wang S; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China. Electronic address: 391912351@qq.com., Cheng H; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China. Electronic address: chengh0920@163.com., Zeng X; NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China. Electronic address: zxf2004033@163.com.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2023 Dec; Vol. 182, pp. 114196. Date of Electronic Publication: 2023 Nov 20.
DOI: 10.1016/j.fct.2023.114196
Abstrakt: α-Amanitin, the primary lethal toxin of Amanita, specifically targets the liver, causing oxidative stress, hepatocyte apoptosis, and irreversible liver damage. As little as 0.1 mg/kg of α-amanitin can be lethal for humans, and there is currently no effective antidote for α-amanitin poisoning. Cannabidiol is a non-psychoactive natural compound derived from Cannabis sativa that exhibits a wide range of anti-inflammatory, antioxidant, and anti-apoptotic effects. It may play a protective role in preventing liver damage induced by α-amanitin. To investigate the potential protective effects of cannabidiol on α-amanitin-induced hepatocyte apoptosis and oxidative stress, we established α-amanitin exposure models using C57BL/6J mice and L-02 cells in vitro. Our results showed that α-amanitin exposure led to oxidative stress, apoptosis, and DNA damage in both mouse hepatocytes and L-02 cells, resulting in the death of mice. We also found that cannabidiol upregulated the level of Nrf2 and antioxidant enzymes, alleviating apoptosis, and oxidative stress in mouse hepatocytes and L-02 cells and increasing the survival rate of mice. Our findings suggest that cannabidiol has hepatoprotective effects through the regulation of Nrf2 and antioxidant enzymes and may be a potential therapeutic drug for Amanita poisoning.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE