Figure 1 Schematic overview of common mechanisms of DILI

Drugs are metabolized in the liver to generate reactive metabolites, which GSH and increase ROS, thereby triggering oxidative stress. This is followed by mitochondrial dysfunction-characterized by ATP depletion, opening of the PTP and/or MOMP, Cyt c release, and activation of the caspase cascade-ultimately leading to cell death. In addition, some drugs inhibit transporters such as the BSEP, causing intracellular bile acid accumulation and cholestatic toxicity. Meanwhile, drug-protein adducts and DAMP activate inflammatory and immune responses, promoting immune cell recruitment and exacerbating hepatocellular injury.