Li R1, Liu F1, Chang Y1, Ma X1, Li M1, Li C2, Shi C1, He J1, Li Y1, Li Z1, Lin Y1, Han Q1, Zhao Y1, Wang D1.

Toxicol Mech Methods. 2017 May 2:1-7

Abstract

Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1 (GSTA1) plays a significant role in the metabolism of APAP. Primary mouse hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and determine whether GSTA1 could be a prognostic marker in vitro. A significant increase (p?<?.05) in GSTA1 in cell culture supernatant was detected at 6?h after APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) showed marked differences (p?<?.05) at 8?h after APAP exposure, 2?h later than GSTA1. Furthermore, GSTA1 increased in a dose-dependent manner with APAP treatment. GSTA1 increased significantly (p?<?.05) at a concentration of 5.0?mmol/L APAP, while the marked changes in ALT, AST and other indexes were undetectable until the concentration of APAP reached 7.5?mmol/L. These results suggest that increased GSTA1 can be more sensitive than ALT and other indexes as a marker of APAP-induced hepatic injury, which provide novel diagnostic index for APAP-induced hepatic injury and supply valuable information to further understand the pathogenesis of liver damage.