title: Protective effect of nitric oxide synthase inhibition or antioxidants on brain oxidative damage caused by intracerebroventricular arginine administration.
abstract: We have previously demonstrated that acute arginine administration induces oxidative stress and compromises energy metabolism in rat hippocampus. In the present study, we initially investigated the effect of intracerebroventricular infusion of arginine (0.1, 0.5 and 1.5 mM solution) on Na(+),K(+)-ATPase activity and on some parameters of oxidative stress, namely thiobarbituric acid-reactive substances (TBA-RS) and total radical-trapping antioxidant parameter (TRAP) in the hippocampus of rats. Results showed that 1.5 mM arginine solution significantly increases TBA-RS and reduces Na(+),K(+)-ATPase activity and TRAP in the rat hippocampus. We also evaluated the influence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), and antioxidants, namely alpha-tocopherol plus ascorbic acid, on the effects elicited by arginine on Na(+),K(+)-ATPase activity, TBA-RS and TRAP. Results showed that treatment with alpha-tocopherol plus ascorbic acid per se did not alter these parameters but prevented these effects. Furthermore, intracerebroventricular infusion of L-NAME prevented the inhibition caused by arginine on Na(+),K(+)-ATPase activity, as well as the increased of TBA-RS. Our findings indicate that intracerebroventricular infusion of arginine induces oxidative stress in rat hippocampus and that the inhibition of Na(+),K(+)-ATPase activity caused by this amino acid was probably mediated by NO and/or its derivatives ONOO(-) and/or other free radicals. Finally, we suggest that the administration of antioxidants should be considered as an adjuvant therapy to specific diets in hyperargininemia.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Delwing
authors.forename: Daniela
authors.initials: D
authors.lastname: Delwing
authors.forename: Caren S
authors.initials: CS
authors.lastname: Bavaresco
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D000578:Amidines / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001120:Arginine / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000627:therapeutic use; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024502:alpha-Tocopherol / Q000627:therapeutic use
chemical_list: D000578:Amidines; D000975:Antioxidants; D004791:Enzyme Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; C046728:2,2'-azobis(2-amidinopropane); D001120:Arginine; D000254:Sodium-Potassium-Exchanging ATPase; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D019331:NG-Nitroarginine Methyl Ester