ABSTRACT
I. INTRODUCTION Three main mechanisms are responsible for drug-induced liver injury. The most frequent mechanism is the formation of reactive drug metabolites that can be directly toxic or cause immune reactions (1,2). Another is drug-induced impairment of mitochondrial function, which may decrease fat oxidation (causing steatosis) and/or energy production (causing cell dysfunction or cell death) (3-7). A third mechanism involves the opening of the mitochondrial permeability transition pore (MPTP), causing necrosis or apoptosis. Although this permeability transition can be triggered by direct or indirect effects of the parent drug on mitochondria (8,9), it is most frequently caused by the formation of reactive metabolites, which can trigger MPTP opening through either direct toxicity or immune reactions (8,9). Thus, even when hepatotoxicity is initially due to the formation of reactive metabolites, mitochondrial injury plays a major role in the final mechanism of cell death (8,9). Therefore, most forms of drug-induced liver lesions initially or secondarily involve mitochondrial injury (9).
