Evaluation and Study of Patho-Physiological Role of Glucocorticoid Receptor (Gr) Ligands in Acetaminophen-Induced Liver Injury in Mice

Abstract

Stress elicited by various drugs and psychosocial components is extensively prevalent globally. Glucocorticoid receptors control different features of lipid metabolism and lipoproteins in the liver. Acetaminophen or paracetamol is a broadly used antipyretic and analgesic drug. Overdose of acetaminophen causes centrilobular necrosis and fibrosis by generating oxidative stress. This experimental study was conducted to evaluate alone as well as combined systemic effects of glucocorticoid receptor (GR) ligands, Mifepristone (GR antagonist), and Dexamethasone (GR agonist) on oxidative damage and liver injury induced by acetaminophen. Evaluation of parameters of liver functions showed a substantial increase in AST ALT levels accompanied by elevation in TOS and reduction in TAC in the APAP-induced hepatotoxic group. While the groups that received dexamethasone, RU-486, and Dex+RU-486 as pretreatment significantly decreased the ALT, AST, and TOS levels compared to the toxic group (APAP). The protective effects of glucocorticoid receptor ligands in APAP-induced liver injury were further verified by histopathological examination. However, additional studies are necessary to illustrate the hepato-protective efficacy, safety profile, basic underlying process of protection, and therapeutic applications of glucocorticoid receptor ligands.