Lipopolysaccharide protects against acetaminophen-induced hepatotoxicity by reducing oxidative stress via the TNF- α/TNFR1 pathway.

Lipopolysaccharide protects against acetaminophen-induced hepatotoxicity by reducing oxidative stress via the TNF-α/TNFR1 pathway. Biochem Biophys Res Commun. 2019 Apr 10;: Authors: Zhao S, Sheng D, Shi R, Jing Y, Jiang J, Meng Y, Fu Z, Hou X, Liu W, Yang X, Li R, Han Z, Wei L Abstract Robust evidence suggested that gut-derived lipopolysaccharide (LPS) plays a significant role in various liver injury diseases; however, the role of gut-derived LPS in acetaminophen (APAP) overdose-induced acute liver injury remains unclear. The present study aimed to investigate the effect of gut-derived LPS on APAP-induced liver injury. Our results revealed that reduction of gut-derived LPS using multiple antibiotics could significantly exacerbate APAP-induced liver injury and increase mortality in mice. By contrast, pretreatment with exogenous LPS could reverse APAP-induced liver hepatotoxicity in mice and rats. We observed that TNF-α secretion in the liver was significantly increased after LPS pretreatment. In addition, depletion of TNF-α or TNFR1 inhibited the protective effects of LPS against APAP-induced hepatotoxicity, which indicated that the TNF-α/TNFR1 pathway was required to protect against APAP-induced liver injury. Mechanistically, LPS reduces oxidative stress by upregulating the expression of hepatic GSH, reducing MDA levels in liver tissues, and upregulating the expression of several antioxidant genes after APAP injection. However, t...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research