Intrastriatal hypoxanthine administration affects Na+,K+-ATPase, acetylcholinesterase and catalase activities in striatum, hippocampus and cerebral cortex of rats

The aim of this study was to investigate the effects of a single intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch–Nyhan disease, on Na+,K+-ATPase, acetylcholinesterase and catalase activities in striatum, cerebral cortex and hippocampus of rats at different post-infusion periods. Adult Wistar rats were divided in two groups: (1) vehicle-injected group (control) and (2) hypoxanthine-injected group. For Na+,K+-ATPase activity determination, the animals were sacrificed 3 h, 24 h and 7 days after drug infusion. For the evaluation of acetylcholinesterase and catalase activities, the animals were sacrificed 30 min, 3 h, 24 h and 7 days after hypoxanthine infusion. Results show regional and time dependent effects of hypoxanthine on Na+,K+-ATPase, acetylcholinesterase and catalase activities. The in vitro effect of hypoxanthine on the same enzymes in striatum was also investigated. Results showed that hypoxanthine inhibited Na+,K+-ATPase, but not the activities of acetylcholinesterase and catalase in rat striatum. We suggest that these modification on cerebral biochemical parameters (Na+,K+-ATPase, acetylcholinesterase and catalase activities) induced by intrastriatal administration of hypoxanthine in all cerebral structures studied, striatum, hippocampus and cerebral cortex, could be involved in the pathophysiology of Lesch–Nyhan disease.