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Given the fact that APAP toxicity is initiated by metabolism through cytochrome P450 enzymes, any subtle interference with the formation of reactive metabolite NAPQI and accumulation of APAP protein adducts (APAP-ADs) can produce a profound impact on the outcome of APAP-induced liver injury

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This suggests that perhaps a common mechanism exists with the R-domain as well, although further biophysical and computational studies will be needed to uncover how

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