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In addition, p -cresol is also likely to deplete GSH as, like APAP, it is a substrate for oxidative metabolism, forming reactive metabolites (RMs) via CYP P450-mediated metabolism (both a quinone methide via CYP2D6, 2C19, 1A2, 1A1, and 2E1 and a 4-methyl- o -hydroquinone that is further oxidized to 4-methyl-1,2-benzoquinone, mainly via CYP2E1 but also CYP1A1, 1A2, and 2D6)36 potentially reducing the ability of the host to simultaneously detoxify APAP-derived RMs

The combined approach has been also suggested by animal model studies

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