Effects of suramin on acetaminophen-induced acute liver injury in mice and the mechanism
10.7644/j.issn.1674-9960.2024.08.008
- VernacularTitle:苏拉明改善对乙酰氨基酚诱导小鼠急性肝损伤的作用及机制研究
- Author:
Xu CHEN
1
;
Huiru LIU
;
Ting WANG
;
Shensi XIANG
;
Yiqun ZHAN
;
Xiaoming YANG
;
Guangming REN
Author Information
1. 军事科学院军事医学研究院,北京 100850
- Keywords:
acetaminophen;
drug-induced liver injury;
suramin;
oxidative stress;
JNK signaling pathway
- From:
Military Medical Sciences
2024;48(8):608-613
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and mechanism of suramin(Sur)in acetaminophen(APAP)-induced acute liver injury in mice.Methods 8-10 weeks old C57BL/6J mice were randomly divided into the APAP group and APAP+Sur group(20 mg/kg suramin was injected 1 h before).After 18 hrs of fasting,400 mg/kg APAP was injected intraperitoneally to establish a mouse model of acute liver failure and the survival rate was recorded.An acute liver injury model of mice was established via intraperitoneal injection of 300 mg/kg APAP(other conditions remained unchanged).A control group was also established,with liver tissues and serum collected at 0,2,and 12 hours post-APAP treatment.ELISA and CBA techniques were adopted to detect the release of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum and the secretion of inflammatory factors.H&E staining and immunohistochemistry were used to detect liver tissue necrosis and inflammatory cell infiltration.DCFA-DH and ELISA techniques were used to detect the levels of reactive oxygen species(ROS),malondialdehyde(MDA)and glutathione(GSH)in liver tissues.Western blotting was employed to assess the activation of the JNK signaling pathway in liver tissues.Results Suramin treatment improved the survival rate of APAP-induced mice,reduced the release of transaminases and inflammatory factors in serum,and alleviated APAP-induced liver cell necrosis and inflammatory cell infiltration in the liver.Suramin treatment delayed APAP-induced GSH depletion in the liver,reduced MDA and ROS levels,and inhibited JNK pathway activation.Conclusion This study has confirmed the protective effect of suramin against acetaminophen-induced acute liver injury in mice.The mechanism is potentially related to oxidative stress and inflammation.
