Protective effect of N- acetylcysteine on liver damage caused by α -amanita toxin poisoning by regulating mitochondrial dynamic imbalance
10.3760/cma.j.cn114656-20241212-00869
- VernacularTitle:N-乙酰半胱氨酸调节线粒体动力学失衡对α-鹅膏毒肽中毒肝损害的保护作用
- Author:
Yun CHEN
1
;
Jin WU
;
Yuanlan LU
;
Yu NI
;
Jie HU
;
Jiangshan ZHAN
Author Information
1. 遵义医科大学附属医院急诊科，遵义 563000
- Keywords:
α-amanita toxin peptide;
Liver injury;
Mitochondrial dynamics;
N- acetylcysteine;
Oxidative stress;
ICR mice
- From:
Chinese Journal of Emergency Medicine
2025;34(10):1396-1402
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of N-acetylcysteine (NAC) against α-amanitin (α-AMA)-induced liver injury via regulation of mitochondrial dynamic imbalance.Methods:Thirty-two ICR mice were randomly (random number) assigned to four groups ( n = 8 per group): normal control, NAC control, α-AMA poisoning, and α-AMA + NAC treatment group. After modeling, behavioral changes were observed and survival curves were plotted. Liver function markers and oxidative stress indicators were measured using ELISA. Pathological damage in liver tissue was examined, and mitochondrial ultrastructural changes were observed via transmission electron microscopy, followed by mitochondrial injury scoring. Survival rates were analyzed using the Kaplan–Meier method. One-way ANOVA was used for intergroup comparisons, followed by pairwise comparisons. Results:Compared with the control group, α-AMA intoxication significantly reduced survival rates and increased serum ALT and AST levels ( P < 0.05). Liver tissues exhibited disordered hepatic cord arrangement, cytoplasmic loosening, and edema. Mitochondria showed moderate to severe swelling, cristae fragmentation, matrix dissolution, and vacuolation, along with increased injury scores ( P < 0.05). Oxidative markers MDA and ROS were elevated, while antioxidant enzymes SOD and CAT were decreased (all P < 0.05). Mitochondrial activity was impaired, expression of fusion proteins OPA1, MFN1, and MFN2 was downregulated, and fission protein DRP1 was upregulated (all P < 0.05). Compared with the α-AMA group, NAC treatment significantly improved survival, reduced ALT and AST levels ( P < 0.05), alleviated pathological and mitochondrial ultrastructural damage, decreased MDA and ROS, increased SOD and CAT (all P < 0.05), enhanced mitochondrial activity, upregulated OPA1, MFN1, and MFN2, and downregulated DRP1 (all P < 0.05). No significant differences were observed between the normal and NAC control groups. Conclusions:NAC may attenuate α-AMA-induced acute liver injury by maintaining mitochondrial dynamic homeostasis.
