Post-Exposure 3-Methyladenine Is Associated with Lower Indices of Hepatic Injury and Fibrotic Remodeling After Chronic Sodium Arsenite Exposure in Mice

This study aimed to evaluate 3-methyladenine (3-MA) as a post-exposure intervention for arsenic-associated hepatic injury and fibrotic remodeling, motivated by its reported antifibrotic effects. Female C57BL/6J mice received sodium arsenite via drinking water for 20 weeks at a nominal target dose of 1.08 mg/kg body weight/day, based on our group’s previous experiments. The remaining exposed mice were randomized to intraperitoneal vehicle (n = 8) or 3-MA (n = 9; 5 μg/g body weight), administered twice weekly for 4 weeks after arsenic withdrawal. The 3-MA dose and frequency were based on a published carbon tetrachloride-induced fibrosis study. Serum markers, liver histology, and hepatic proteins were assessed. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) trajectories differed between groups, with lower Day-28 activities after 3-MA; the ALT difference persisted after baseline adjustment (p = 0.0011). Day-28 serum hyaluronic acid, N-terminal propeptide of type III procollagen, tumor necrosis factor-α, collagen volume fraction, and α-smooth muscle actin immunoreactivity were also lower than with vehicle. These differences were accompanied by changes in nuclear factor-kappa B- and autophagy-related proteins. Post-exposure 3-MA was associated with lower hepatic injury and fibrotic remodeling indices, but an autophagy-dependent mechanism and within-animal fibrosis regression were not established.