title: Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity.
abstract: Acetaminophen (APAP) is a well-known analgesic and antipyretic drug. It is considered to be safe when administered within its therapeutic range, but in cases of acute intoxication, hepatotoxicity can occur. APAP overdose is the leading cause of acute liver failure in the northern hemisphere. Historically, studies on APAP toxicity have been focused on liver, with alterations in brain function attributed to secondary effects of acute liver failure. However, in the last decade the pharmacological mechanism of APAP as a cannabinoid system modulator has been documented and some articles have reported "in situ" toxicity by APAP in brain tissue at high doses. Paradoxically, low doses of APAP have been reported to produce the opposite, neuroprotective effects. In this paper we present a comprehensive, up-to-date overview of hepatic toxicity as well as a thorough review of both toxic and beneficial effects of APAP in brain.
authors.affiliation: Instituto de Investigaciones Farmacológicas (ININFA), Facultad de Farmacia y Bioquímica, CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina; Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: cghanem@ffyb.uba.ar.
authors.forename: Carolina I
authors.initials: CI
authors.lastname: Ghanem
authors.affiliation: Cátedra de Química Biológica Patológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológica (IQUIFIB), UBA-CONICET, Buenos Aires, Argentina.
authors.forename: María J
authors.initials: MJ
authors.lastname: Pérez
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, United States.
authors.forename: José E
authors.initials: JE
authors.lastname: Manautou
authors.affiliation: Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, Universidad Nacional de Rosario, Rosario, Santa Fe, Argentina.
authors.forename: Aldo D
authors.initials: AD
authors.lastname: Mottino
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology* / Q000633:toxicity*; D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000082:Acetaminophen; D000111:Acetylcysteine
keywords: Acetaminophen; Caspase; DAMPs; Hepatic toxicity; Necroptosis; trpv1