Acetaminophen Manuscript

This page is being prepared to submit a manuscript for peer review and publication in the Journal of Chemical Research in Toxicology by Matthew Simonson. The goal of this work is to provide foundational evidence for a mechanism of hepatotoxicity caused by radical polymerization of Acetaminophen within the liver as opposed to soley a mechanism of two electron oxidation into NAPQI.

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Abstract

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Acetaminophen (APAP) is a common analgesic and an active ingredient in many painkillers such as Tylenol and Percocet. Upon overdose, APAP can lead to toxicity in the liver, which accounts for a striking proportion of acute liver failures in the United States annually. Considering the potential for APAP induced hepatotoxicity, our research group has analyzed APAP and its tendency to oxidize into reactive products through both enzymatic and electrochemical methods of in vitro oxidation. Characterization of these APAP oxidation products were carried out using electron spin resonance (ESR), quadruple time-of-flight mass spectrometry (qTOF-MS), 400 MHz proton nuclear magnetic resonance (H-NMR), and cyclic voltammetry (CV). Our findings purport that APAP prefers to oxidize through a mechanism of radical polymerization, which lends insight into the oxidation cascade that occurs as the liver oxidizes APAP during times of overdose.

Introduction

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The commonly accepted mechanism of Acetaminophen (APAP) induced hepatotoxicity is the two electron oxidation of APAP into the reactive metabolite NAPQI via Cytochrome P450 enzymes ().

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