Context-Dependent Redox Mechanisms in Drug-Induced Liver Injury: Shared and Distinct Roles Across Hepatocellular and Cholestatic Phenotypes

Oxidative stress and redox dysregulation are widely implicated in drug-induced liver injury (DILI), yet their roles vary considerably according to the initiating insult, cellular context, and stage of injury. Rather than representing a single pathogenic mechanism, redox disturbances may function as initiating contributors, injury amplifiers, adaptive responses, or downstream consequences of tissue injury. This review examines these context-dependent roles using hepatocellular and cholestatic DILI as complementary settings for distinguishing shared and divergent redox mechanisms. We discuss how mitochondrial oxidant stress, glutathione- and thioredoxin-dependent defenses, nuclear factor erythroid 2-related factor 2 (NRF2)-mediated adaptation, redox-sensitive signaling, lipid peroxidation, and inflammatory oxidants occupy different positions within the injury cascade across representative DILI settings. This review focuses particularly on the sources, spatial organization, timing, molecular targets, and consequences of redox events, all of which are considered together with their magnitude. This perspective may help reconcile apparently inconsistent findings across experimental models and improve the mechanistic interpretation of redox biomarkers and therapeutic interventions in DILI.