ABSTRACT
There are three main mechanisms for drug-induced liver injury. The most frequent mechanism
is the formation of reactive drug metabolites that can be directly toxic or can cause immune
reactions (1,2). The other is drug-induced impairment of mitochondrial function, which may
decrease fat oxidation (thus causing steatosis) and/or energy production (thus causing cell
dysfunction or cell death) (3-7). A third mechanism involves the opening of the mitochondrial
permeability transition (MPT) pore, causing either necrosis or apoptosis. Although a few parent
drugs can trigger this transition (8,9), it is more commonly caused by reactive metabolites,
which can lead to MPT either through direct toxicity or through immune reactions (8,9). Thus,
even when liver injury is initially due to the formation of reactive metabolites, mitochondrial
damage plays a major role in the final mechanisms of cell death (8,9). Therefore, most forms of
drug-induced liver lesions initially or secondarily involve mitochondrial injury (9).
