Effect of methane on acetaminophen-induced acute liver injury in mice and role of autophagy
10.3760/cma.j.cn131073.20201102.00316
- VernacularTitle:甲烷对对乙酰氨基酚诱发小鼠急性肝损伤的影响及自噬在其中的作用
- Author:
Ting WANG
1
;
Qian XIANG
;
Ying WANG
;
Jinjun BIAN
Author Information
1. 海军军医大学附属长海医院麻醉科，上海 200433
- Keywords:
Methane;
Acetaminophen;
Chemical and drug induced liver injury;
Autophagy
- From:
Chinese Journal of Anesthesiology
2021;41(3):323-326
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of methane on acetaminophen-induced acute liver injury (ALI) in mice and the role of autophagy.Methods:Forty clean-grade SPF healthy adult male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), group ALI, methane-rich saline group (group MS) and methane-rich saline plus 3-methyladenine (3-MA) group (group MS+ 3-MA). Acetaminophen 300 mg/kg was injected intraperitoneally to establish ALI model.Group MS was injected intraperitoneally with methane-rich saline 10 ml/kg immediately after establishing the model and at 12 h after establishing the model.Group MS+ 3-MA was injected intraperitoneally with methane-rich saline 10 ml/kg and autophagy inhibitor 3-MA 30 mg/kg immediately after establishing the model and was injected intraperitoneally with methane-rich saline 10 ml/kg at 12 h after establishing the model.The equal volume of sterile saline was given intraperitoneally at the same time points in C and ALI groups.At 24 h after establishment of the model, blood samples from the eyeball were taken for measuring concentrations of alanine transaminase (ALT) and aspartate transaminase (AST) in serum (using biochemistry analyzer) and the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum (using enzyme-linked immunosorbent assay). The animals were then sacrificed and liver tissues were removed for determination of microtubule-associated protein 1 light chain 3 (LC3) and p62 (by Western blot) and for the examination of the number of autophagosomes (under a transmission electron microscope). Results:Compared with group C, the concentrations of ALT, AST, TNF-α and IL-6 in serum were significantly increased, LC3Ⅱ/LC3Ⅰ ratio was increased, expression of p62 was up-regulated, and the number of autophagosomes was increased in liver tissues in ALI, MS and MS+ 3-MA groups ( P<0.05). Compared with group ALI, the concentrations of ALT, AST, TNF-α and IL-6 in serum were significantly decreased, LC3Ⅱ/LC3Ⅰ ratio was increased, expression of p62 was down-regulated, and the number of autophagosomes in liver tissues was increased in group MS, and AST concentration in serum was decreased and LC3Ⅱ/LC3Ⅰ ratio was increased in group MS+ 3-MA ( P<0.05). Compared with group MS, the concentrations of ALT, AST, TNF-α and IL-6 were significantly increased, the LC3 II/LC3 I ratio and the number of autophagosomes were decreased in lung tissues in group MS+ 3-MA ( P<0.05). Conclusion:The mechanism by which methane can reduce acetaminophen-induced ALI is related to enhancement of the level of autophagy in liver cells in mice.
