Biochemical effects of pretreatment with vitamins E and C in rats submitted to intrastriatal hypoxanthine administration.
We previously demonstrated that intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, inhibited Na+,K+-ATPase activity and induced oxidative stress in rat striatum. In the present study, we evaluated the action of vitamins E and C on the biochemical alteration induced by hypoxanthine administration on Na+,K+-ATPase, TBARS, TRAP, as well as on superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities in striatum of adult rats. Animals received pretreatment with vitamins E and C or saline during 7 days. Twelve hours after the last injection of vitamins or saline, animals were divided into two groups: (1) vehicle-injected group and (2) hypoxanthine-injected group. For all parameters investigated in this research, animals were sacrificed 30 min after drug infusion. Results showed that pretreatment with vitamins E and C prevented hypoxanthine-mediated effects on Na+,K+-ATPase, TBARS and antioxidant enzymes (SOD, CAT and GPx) activities; however the reduction on TRAP was not prevented by these vitamins. Although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins might serve as an adjuvant therapy in order to avoid progression of striatal damage in patients affected by Lesch-Nyhan disease.
Bavaresco
Caren Serra
CS
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.
Chiarani
Fabria
F
Kolling
Janaína
J
Netto
Carlos Alexandre
CA
de Souza Wyse
Angela Terezinha
AT
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018450:Disease Progression; D005609:Free Radicals / Q000378:metabolism; D019271:Hypoxanthine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D007926:Lesch-Nyhan Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016896:Treatment Outcome; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D005609:Free Radicals; C000606290:SOD1 protein, human; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D019271:Hypoxanthine; D002374:Catalase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000254:Sodium-Potassium-Exchanging ATPase; D001205:Ascorbic Acid