A new twist to an old tale: Novel insights into the differential toxicities of acetaminophen and its regioisomer N-acetyl-meta-aminophenol (AMAP)

摘要

Within the toxicological community, it is generally accepted that, whereas the widely used analgesic and antipyretic drug acetaminophen (N-acetyl-para-aminophe-nol) causes dose-dependent liver toxicity in humans and in various animal species, its regioisomer N-acetyl-meta-aminophenol (AMAP) does not. Liver injury caused by acetaminophen is initiated by cytochrome P450 (CYP)-mediated bioactivation to N-acety-para-benzoquinonei-mine (NAPQI), which is a chemically reactive intermediate that is formed at high levels following overdosage and triggers a complex cascade of events, which ultimately result in hepatocellular necrosis (Hinson et al. 2010; see Fig. 1).