title: Antioxidant effect of acetylsalicylic and salicylic acid in rat brain slices subjected to hypoxia.
abstract: Acetylsalicylic acid (ASA) reduces the incidence of ischemic stroke mainly through its antithrombotic action; however, it also has a direct neuroprotective effect. The present study was designed to evaluate the effect of ASA on oxidative stress and the activity of nitric oxide synthase (NOS) in an in vitro model of hypoxia in rat brain slices. Rat brain slices were perfused with nitrogen (hypoxia) for a maximum of 120 min, after which we measured lipid peroxidation, glutathione levels, glutathione-related enzyme activities, and constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) activities. In brain tissue subjected to hypoxia, ASA reduced oxidative stress and iNOS activity (all increased by hypoxia), but only when used at higher concentrations. The effects of salicylic acid (SA) were similar but more intense than were those of ASA. After oral administration, the effect of SA was much greater than that of ASA, and the decrease in cell death with SA was seen much more clearly. In view of the greater effect of SA compared to ASA on changes in oxidative stress parameters in a model of hypoxia, and higher brain concentrations of SA when it is administered alone than when ASA is given (undetectable levels), we conclude that SA plays an important role in the cytoprotective effect in brain tissue after ASA administration.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
authors.forename: J P
authors.initials: JP
authors.lastname: De La Cruz
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Guerrero
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: González-Correa
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
authors.forename: M M
authors.initials: MM
authors.lastname: Arrebola
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Sánchez de la Cuesta
mesh_terms: D000818:Animals; D001241:Aspirin / Q000097:blood / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000097:blood / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020156:Salicylic Acid / Q000097:blood / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione; D020156:Salicylic Acid; D001241:Aspirin