Combination of monoammonium glycyrrhizinate and cysteine hydrochloride ameliorated lipopolysaccharide/galactosamine-induced acute liver injury through Nrf2/ARE pathway

• Published in: European journal of pharmacology Vol. 882; p. 173258
• Main Authors: Chu, Shifeng, Niu, Ziquan, Guo, Qingxin, Bi, Haozhi, Li, Xinyu, Li, Fangfang, Zhang, Zhao, He, Wenbin, Cao, Peng, Chen, Naihong, Sun, Xiaoyun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.09.2020
• Subjects: Acute liver injury; Animals; Antioxidant Response Elements; Cells, Cultured; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - genetics; Chemical and Drug Induced Liver Injury - metabolism; Cysteine; Cysteine - pharmacology; Cysteine - therapeutic use; Cytokines - genetics; Drug Combinations; Galactosamine; Glutathione - metabolism; Glycyrrhizic Acid - pharmacology; Glycyrrhizic Acid - therapeutic use; Heme Oxygenase-1 - genetics; Hepatocytes - drug effects; Hepatocytes - metabolism; Inflammation; Lipopolysaccharides; Liver - drug effects; Liver - metabolism; Male; Malondialdehyde - metabolism; Mice, Inbred C57BL; Mice, Knockout; Monoammonium glycyrrhizinate; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative damage; Peroxidase - metabolism; Signal Transduction - drug effects; Superoxide Dismutase - metabolism; Monoammonium glycyrrhizinate; Cysteine; Inflammation; Acute liver injury; Oxidative damage; Nrf2
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2020.173258

Combination of monoammonium glycyrrhizinate and cysteine hydrochloride (MG-CH) has been used for treatment of chronic liver damage in clinic for several years, however, the effect of MG-CH on acute liver injury (ALI) is still obscure. In this study, we aimed to investigate the effect of MG-CH on ALI induced by co-injection of lipopolysaccharide (LPS) and d-galactosamine (GalN). Our results found that MG-CH produced the optimal therapeutic effect at the ratio of 2:1, as manifested by the increased survival percentage, decreased ALT and AST level and improved hepatic pathology. Both oxidative stress and inflammation induced by LPS/GalN were attenuated by MG-CH. Mechanism study showed that MG-CH promoted the nuclear accumulation of Nrf2 and its transcriptional activity, as well as improved Nrf2-target genes’ expression. It was also found that activation of Nrf2 is dependent on the MG, not CH. Blockade of Nrf2 abolished the anti-inflammatory effect of MG-CHinduced by LPS/GalN, while inhibition of NFκB showed no effect on its anti-oxidative effect, though the inhibited phosphorylation of IκB and NFκB were detected in liver. The protective effect of MG-CH against ALI was abolished in Nrf2-/- mice. All of these results suggested that MG-CH ameliorated LPS/GalN induced ALI through Nrf2/ARE pathway.