Intrastriatal injection of hypoxanthine alters striatal ectonucleotidase activities: A time-dependent effect

• Published in: Brain research 2008-11, Vol.1239, p.198-206
• Main Authors: Bavaresco, Caren S, Chiarani, Fabria, Kolling, Janaina, Ramos, Denise B, Cognato, Giana P, Bonan, Carla D, Bogo, Maurício R, Sarkis, João J.F, Netto, Carlos A, Wyse, Angela T.S
• Format: Article
• Language: English
• Subjects: 5'-Nucleotidase - metabolism; Adenosine Triphosphatases - metabolism; Animals; Antigens, CD - metabolism; Apyrase - metabolism; Ascorbic Acid - administration & dosage; Ascorbic Acid - pharmacology; Biochemistry and metabolism; Biological and medical sciences; Central nervous system; Central Nervous System Agents - administration & dosage; Central Nervous System Agents - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - enzymology; Corpus Striatum - metabolism; Ectonucleotidase; Fundamental and applied biological sciences. Psychology; Hydrolysis - drug effects; Hypoxanthine - administration & dosage; Hypoxanthine - pharmacology; Intrastriatal hypoxanthine administration; Lesch Nyhan disease; Male; Neurology; NTPDase; Nucleotides - metabolism; Oxidative stress; Pyrophosphatases - metabolism; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances - metabolism; Time Factors; Vertebrates: nervous system and sense organs; Vitamin E - administration & dosage; Vitamin E - pharmacology; Vitamins - administration & dosage; Vitamins - pharmacology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.08.015

Abstract The aim of this study was to investigate the effects of intrastriatal injection of hypoxanthine on ectonucleotidase (E-NTPDases and ecto-5′-nucleotidase) activities and expressions in the striatum of rats. The effect of pre-treatment with vitamins E and C on the effects elicited by this oxypurine on enzymatic activities and on thiobarbituric reactive substances (TBARS) was also investigated. The effect of pre-incubation with hypoxanthine on nucleotide hydrolysis in striatum homogenate was also determined. Adult Wistar rats were divided into (1) control and (2) hypoxanthine-injected groups. For ectonucleotidase activity determination, the animals were sacrificed at 30 min, 24 h and 7 days after drug infusion. For the evaluation of the expression of NTPDase 1–3 and also ecto-5′-nucleotidase, TBARS assay and the influence of the pre-treatment with vitamins on ectonucleotidase activities, the animals were sacrificed 24 h after hypoxanthine infusion. Results show that hypoxanthine infusion significantly inhibited ectonucleotidase activities and increased TBARS only 24 h after administration. Pre-treatment with vitamins was able to prevent these effects. Moreover, ecto-5′-nucleotidase expression was increased (80%) at 24 h after hypoxanthine infusion. We suggest that these hypoxanthine-induced biochemical modifications could, at least in part, participate in the pathophysiology of Lesch Nyhan disease.