Acetaminophen-induced hepatotoxicity.

By L. James, P. Mayeux, J. Hinson. Drug Metabolism And Disposition, 2003

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High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes. (2001, background): “Covalent binding of reactive APAP metabolites to cellular proteins seems to be an important process in the induction of hepatotoxicity (Cohen et al., 1998).”
Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches (2001, background): “Thus, as described more in detail in Section IV, in mice, rats, and humans, an overdose of PAR may result in severe centrilobular hepatic necrosis (Hinson et al., 1981; Prescott, 1983; Hinson et al., 1990; Vermeulen et al., 1992).”