Toxicological sciences : an official journal of the Society of Toxicology
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Acetaminophen (APAP) overdose is the most frequent cause of adult acute liver failure. Susceptibility or resistance to APAP toxicity is most likely accounted for by the interplay of several factors. One factor important in multiple different chronic liver diseases that may play a role in APAP toxicity is elevated hepatic iron. ⋯ Further analysis showed that the levels of CYP2E1 and CYP1A2 were not significantly different in TMHF-treated compared with control mice. However, the magnitude of depletion of glutathione following APAP treatment was considerably less in TMHF-treated mice than in mice fed a control diet. We conclude that a TMHF diet protects mice from moderate transient APAP-induced hepatotoxicity prior to the formation of APAP adducts, and one contributing mechanism is reduction in glutathione depletion.