Cytochrome P450 2E1 should not be neglected for acetaminophen-induced liver injury in metabolic diseases with altered insulin levels or glucose homeostasis

Acetaminophen (APAP) hepatotoxicity is mediated by N-acetyl- p -benzoquinone imine (NAPQI), a highly toxic metabolite generated cytochrome P450 2E1 (CYP2E1). Thus, pathological conditions increasing CYP2E1 activity can favour APAP-induced liver injury, which characterized massive hepatocellular necrosis and secondary sterile inflammation. In recent work, Wang et al. showed that was exacerbated in murine model of type 1 diabetes induced the administration streptozotocin (STZ). Higher particular associated with stronger proinflammatory response resident macrophages. Although authors carried out numerous investigations, they did not study hepatic CYP2E1, nor discussed possible role this enzyme exacerbation APAP hepatotoxicity. However, investigations reported induction STZ-treated rodents, could be to insulinopenia ketosis. This commentary also discusses insulin resistance observed obesity nonalcoholic fatty disease. Investigators studying injury context or hyperinsulinemia are thus encouraged consider as significant player phenotypic changes.