3-Cysteinylacetaminophen is an acetaminophen-protein adduct formed during the metabolism of acetaminophen.[1],[2] 3-Cysteinylacetaminophen has been found in isolated human serum following therapeutic and supratherapeutic doses of acetaminophen and in the presence and absence of hepatotoxicity.[3],[4] In mice, 3-cysteinylacetaminophen decreases renal glutathione (GSH) levels, an effect that can be blocked by the γ-glutamyl inhibitor acivicin.
Reference:
[1]. Yoon, E., Babar, A., Choudhary, M., et al. Acetaminophen-induced hepatotoxicity: A comprehensive update. J. Clin. Transl. Hepatol. 4(2), 131-142 (2016).
[2]. Stern, S.T., Bruno, M.K., Horton, R.A., et al. Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the γ-glutamyl cycle. Toxicol. Appl. Pharmacol. 202(2), 160-171 (2005).
[3]. Heard, K., Green, J.L., Anderson, V., et al. Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing. Br. J. Clin. Pharmacol. 81(3), 562-568 (2016).
[4]. O'Malley, G.F., Mizrahi, F., Giraldo, P., et al. Protein-derived acetaminophen-cysteine can be detected after repeated supratherapeutic ingestion of acetaminophen in the absence of hepatotoxicity. J. Med. Toxicol. 11(3), 317-320 (2015).