title: Acetaminophen-induced liver oxidative stress and hepatotoxicity: influence of Kupffer cell activity assessed in the isolated perfused rat liver.
abstract: The influence of acetaminophen (APAP) treatment (400 mg/kg) on Kupffer cell function was studied in the isolated perfused liver by colloidal carbon infusion, concomitantly with parameters related to oxidative stress (thiobarbituric acid reactants (TBARS) formation and glutathione (GSH) content) and tissue injury (sinusoidal efflux of lactate dehydrogenase (LDH)). APAP led to increased rates of hepatic TBARS formation, GSH depletion, and higher sinusoidal LDH efflux compared to control values, without changes in the basal rate of O2 consumption. In addition, APAP significantly enhanced the rate of carbon uptake by perfused livers and the associated carbon-induced O2 consumption, with carbon-induced LDH effluxes being increased by 411% over control values or by 124% compared to basal LDH release in APAP-treated rats. APAP-induced changes in liver TBARS formation and GSH levels were attenuated by gadolinium chloride (GdCl3) pretreatment, whereas those in carbon uptake, carbon-induced respiration, and LDH efflux were abolished. GdCl3 pretreatment decreased liver O2 consumption irrespectively of APAP treatment, an effect that seems to be due to depression of mitochondrial respiration. It is concluded that APAP intoxication enhances Kupffer cell function as assessed in the intact liver, which may represent an important source of reactive O2 species and chemical mediators conditioning the increased oxidative stress status and the tissue injury which developed.
authors.affiliation: a Programa de Farmacología Molecular y Clínica , Instituto de Ciencias Biomédicas , Facultad de Medicina , Universidad de Chile , Santiago , Chile.
authors.forename: G
authors.initials: G
authors.lastname: Tapia
authors.affiliation: a Programa de Farmacología Molecular y Clínica , Instituto de Ciencias Biomédicas , Facultad de Medicina , Universidad de Chile , Santiago , Chile.
authors.forename: P
authors.initials: P
authors.lastname: Cornejo
authors.affiliation: a Programa de Farmacología Molecular y Clínica , Instituto de Ciencias Biomédicas , Facultad de Medicina , Universidad de Chile , Santiago , Chile.
authors.forename: J
authors.initials: J
authors.lastname: Ferreira
authors.affiliation: a Programa de Farmacología Molecular y Clínica , Instituto de Ciencias Biomédicas , Facultad de Medicina , Universidad de Chile , Santiago , Chile.
authors.forename: V
authors.initials: V
authors.lastname: Fernández
authors.affiliation: a Programa de Farmacología Molecular y Clínica , Instituto de Ciencias Biomédicas , Facultad de Medicina , Universidad de Chile , Santiago , Chile.
authors.forename: L A
authors.initials: LA
authors.lastname: Videla