ascorbic-acid and Lesch-Nyhan-Syndrome

In the present study, we investigate the in vitro effect of hypoxanthine on acetylcholinesterase and butyrylcholinesterase activities in the hippocampus, striatum, cerebral cortex and serum of 15-, 30- and 60-day-old rats. Furthermore, we also evaluated the influence of antioxidants, namely α-tocopherol (trolox) and ascorbic acid, and allopurinol to investigate the possible participation of free radicals and uric acid in the effects elicited by hypoxanthine on these parameters. Acetylcholinesterase and butyrylcholinesterase activities were determined according to Ellman et al. (Biochem Pharmacol 7:88-95, 1961), with some modifications. Hypoxanthine (10.0 μM), when added to the incubation medium, enhanced acetylcholinesterase activity in the hippocampus and striatum of 15- and 30-day-old rats and reduced butyrylcholinesterase activity in the serum of 60-day-old rats. The administration of allopurinol and/or antioxidants partially prevented the alterations caused by hypoxanthine in acetylcholinesterase and butyrylcholinesterase activities in the cerebrum and serum of rats. Data indicate that hypoxanthine alters cholinesterase activities, probably through free radicals and uric acid production since the alterations were prevented by the administration of allopurinol and antioxidants. It is presumed that the cholinesterase system may be associated, at least in part, with the neuronal dysfunction observed in patients affected by Lesch-Nyhan disease. In addition, although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins and allopurinol might serve as an adjuvant therapy to avoid progression of brain damage in patients affected by this disease.

Topics: Acetylcholinesterase; Allopurinol; alpha-Tocopherol; Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; Butyrylcholinesterase; Cholinesterases; Enzyme Inhibitors; Free Radicals; Hypoxanthine; Lesch-Nyhan Syndrome; Rats; Rats, Wistar; Uric Acid

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.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Corpus Striatum; Disease Progression; Free Radicals; Hypoxanthine; Lesch-Nyhan Syndrome; Oxidative Stress; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Superoxide Dismutase; Superoxide Dismutase-1; Thiobarbituric Acid Reactive Substances; Treatment Outcome; Vitamin E

Topics: Adenosine; Adenosine Triphosphate; Allopurinol; Animals; Ascorbic Acid; Female; Humans; Hypoxanthine Phosphoribosyltransferase; Lesch-Nyhan Syndrome; Methylene Blue; Phosphoribosyl Pyrophosphate; Purines; Pyrimidines; Ribosemonophosphates; Uric Acid