Table 1.

Examples of drugs that can cause DILI, the drug metabolizing enzymes and transporters implicated in their toxicity, and the proposed mechanism(s).

Drug (Class)	Toxicity	Implicated DMETs	Mechanism	References
Acetaminophen (Analgesic)	Hepatotoxicity	CYP2E1	↑ NAPQI → ↑ Protein Adducts	(33)
Isoniazid (Anti-tuberculosis)	Hepatotoxicity	CYP2E1, NAT2, GSTM1	Mechanism unclear and controversial (↑ reactive metabolite(s) → ↑ protein adducts?)	(34–38)
Diclofenac (Analgesic)	Hepatotoxicity	UGT2B7, CYP2C8, ABCC2	↓ Glucuronidation → ↑ quinonimines → ↑ cell stress	(39, 40)
Ticlopidine (Anti-platelet)	Hepatotoxicity	CYP2B6 and HLA	Mechanism unclear (immune mechanism?)	(41)
Tolcapone (Anti-Parkinson)	Hepatotoxicity	UGT1A	Mechanism unclear (↓ glucuronidation → ↑ tolcapone → ↑ mitochondrial toxicity?)	(42)
Troglitazone (Anti-diabetic)	Hepatotoxicity/Cholestasis	CYP3A4?, SULT1A3?, UGT?	Mechanisms unclear and controversial ↑ TGZ-sulfate → ↑ BSEP inhibition → ↑ intracellular bile acids → Cholestasis → Mitochondrial toxicity → apoptosis ↑ TGZ → direct mitochondrial toxicity ↑TGZ-quinone → ↑ reactive intermediates (e.g., TGZ-epoxide, open-ringed metabolite, or superoxide anion radical) → ↑ protein adducts, oxidative stress, mitochondrial toxicity	(43–45)
Fialuridine (Antiviral)	Hepatotoxicity	ENT1	Fialuridine is transported into mitochondria by ENT1 → metabolized to its triphosphate derivative → inhibits polymerase-gamma → mitochondrial depletion → lactic acidosis and liver failure	(46, 47)
Bosentan (Anti-hypertensive)	Cholestatic	BSEP	BSEP inhibition → ↑ intracellular bile acids → cholestasis	(48, 49)