title: Reestablishment of ischemia-reperfusion liver injury by N-acetylcysteine administration prior to a preconditioning iron protocol.
abstract: The role of iron (Fe)-induced prooxidant status in Fe preconditioning against ischemia (1 h)-reperfusion (20 h) induced liver injury was assessed using N-acetylcysteine (NAC) (1 g/kg) before Fe (50 mg/kg), given to male Sprague Dawley rats on alternate days during 10 days. IR significantly increased serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, with drastic changes in liver histology, hepatic glutathione depletion, and nuclear factor-κB (NF-κB) p65 diminution (P < 0.05) (ELISA). Fe-induced liver oxidative stress, as evidenced by higher protein carbonyl/glutathione content ratios (P < 0.05) at days 11 and 12 after treatment, was abolished by NAC. Under these conditions, short-term Fe administration exerted significant protection against IR liver injury, as shown by 85% and 60% decreases in IR-induced serum AST and ALT (P < 0.05), respectively, and normalization of hepatic histology, glutathione levels, and NF-κB activation, changes that were suppressed by NAC administration prior to Fe. Results of this study indicate that NAC administration prior to an iron protocol reestablishes IR liver injury, supporting the role of Fe-induced transient oxidative stress in hepatoprotection and its potential clinical application.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla 70000, Santiago 7, Chile.
authors.forename: Virginia
authors.initials: V
authors.lastname: Fernández
authors.forename: Romina
authors.initials: R
authors.lastname: Vargas
authors.forename: Valentina
authors.initials: V
authors.lastname: Castillo
authors.forename: Nicolás
authors.initials: N
authors.lastname: Cádiz
authors.forename: Daniela
authors.initials: D
authors.lastname: Bastías
authors.forename: Sebastián
authors.initials: S
authors.lastname: Román
authors.forename: Gladys
authors.initials: G
authors.lastname: Tapia
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
mesh_terms: D000111:Acetylcysteine / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000009:adverse effects* / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology / Q000627:therapeutic use*; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D007501:Iron; D000111:Acetylcysteine