Combination of monoammonium glycyrrhizinate and cysteine hydrochloride protects mice against acetaminophen-induced liver injury via Keap1/Nrf2/ARE pathway.

Abstract

Acetaminophen (APAP) overdose has been the primary cause of drug-induced liver injury (DILI) in western countries. Monoammonium glycyrrhizinate (MG) is a primary active ingredient from glycyrrhiza. Cysteine hydrochloride (CH) is a component of glutathione (GSH). The study aimed to explore the therapeutical effect of MG-CH against DILI incurred by intragastric APAP. Mice were randomized into eight groups: control, APAP, three groups accepted APAP and the combination of MG and CH (15, 30, 60mg/kg), two groups accepted APAP and MG (40mg/kg) or CH (20mg/kg), moreover, one group received MG-CH (60mg/kg) without APAP. After pretreatment with MG-CH or MG and CH alone for 3 days, mice were administered APAP by oral gavage. The serum and tissue were collected to detect the activities of liver enzymes and evaluate the change of histomorphology and explore the possible mechanism of MG-CH in protecting against DILI. MG-CH pretreatment remarkably alleviated hepatic injury and decreased the activities of ALT, AST, ALP and LDH. The hepatic ROS and MDA contents were decreased, and the level of GSH and GSH-PX activities was increased in the serum. Furthermore, MG-CH improved the expression of Nrf2, HO-1, GCLM and NQO1 to increase antioxidant ability and induce detoxification. The expression of IL-10 suppressing excessive inflammatory responses was enhanced. The study demonstrated that MG-CH had protective effects against DILI induced by APAP and the potential mechanisms were based on inhibiting oxidative stress and activating the Keap1/Nrf2/ARE pathway.