title: Effects of triflusal on oxidative stress, prostaglandin production and nitric oxide pathway in a model of anoxia-reoxygenation in rat brain slices.
abstract: Acetylsalicylic acid (ASA) is the most widely used drug in the prevention of ischemic vascular accidents, mainly because of its antithrombotic effect. Recently, evidence of a neuroprotective effect has appeared. The aim of this study was to evaluate the neuroprotective effect of triflusal, a fluorinated derivative of ASA, in a model of anoxia-reoxygenation in rat brain slices. Rats (n=10 per group) were treated for 7 days with 1, 10 or 50 mg/kg/day p.o. of triflusal or ASA or solvent (control group), then brain slices were obtained and subjected to a period of anoxia followed by 180 min of reoxygenation. We measured oxidative stress parameters (lipid peroxidation, glutathione system), prostaglandins (PGE(2)), nitric oxide pathway activity (NO) (nitrites+nitrates, constitutive and inducible NO synthase activity) and cell death (lactate dehydrogenase (LDH) efflux). Triflusal decreased cell death in rat brain slices subjected to reoxygenation after anoxia by 21%, 42% and 47% with 1, 10 and 50 mg/kg/day, respectively. This effect was proportionately greater than the effect of ASA (0%, 25% and 24%). The antioxidant effects of triflusal on the biochemical mechanisms of cell damage studied here were also greater than the effects of ASA: lipid peroxidation was reduced by 29%, 35% and 36% with triflusal, and 0%, 19% and 29% with ASA. Inducible NO synthase activity was reduced by 25%, 27% and 30% with triflusal, and 0%, 25% and 24% with ASA. Triflusal can be considered an alternative to ASA as a neuroprotective agent, at least in the experimental model of anoxia-reoxygenation used in the present study.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: González-Correa
authors.forename: M M
authors.initials: MM
authors.lastname: Arrebola
authors.forename: I M
authors.initials: IM
authors.lastname: Ureña
authors.forename: A
authors.initials: A
authors.lastname: Guerrero
authors.forename: J
authors.initials: J
authors.lastname: Muñoz-Marín
authors.forename: D
authors.initials: D
authors.lastname: Ruiz-Villafranca
authors.forename: F
authors.initials: F
authors.lastname: Sánchez De La Cuesta
authors.forename: J P
authors.initials: JP
authors.lastname: De La Cruz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D009566:Nitrates; D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D012459:Salicylates; C016167:triflusal; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D001241:Aspirin; D010100:Oxygen