Biochemical effects of pretreatment with vitamins E and C in rats submitted to intrastriatal hypoxanthine administration

• Published in: Neurochemistry international 2008-05, Vol.52 (6), p.1276-1283
• Main Authors: Bavaresco, Caren Serra, Chiarani, Fabria, Kolling, Janaína, Netto, Carlos Alexandre, de Souza Wyse, Angela Terezinha
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Antioxidants - pharmacology; Antioxidants - therapeutic use; Antioxidants defenses; Ascorbic Acid - pharmacology; Ascorbic Acid - therapeutic use; Biological and medical sciences; Catalase - drug effects; Catalase - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - physiopathology; Disease Progression; Free Radicals - metabolism; Fundamental and applied biological sciences. Psychology; Hypoxanthine; Hypoxanthine - antagonists & inhibitors; Hypoxanthine - metabolism; Hypoxanthine - toxicity; Lesch-Nyhan Syndrome - drug therapy; Lesch-Nyhan Syndrome - metabolism; Lesch-Nyhan Syndrome - physiopathology; Lesch–Nyhan; Lipoperoxidation; Na +,K +-ATPase; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase - drug effects; Sodium-Potassium-Exchanging ATPase - metabolism; Superoxide Dismutase - drug effects; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; Thiobarbituric Acid Reactive Substances - metabolism; Treatment Outcome; Vertebrates: nervous system and sense organs; Vitamin E - metabolism; Vitamin E - pharmacology; Vitamin E - therapeutic use; Vitamins E and C
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2008.01.008

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.