PMID- 15829228 OWN - NLM STAT- MEDLINE DCOM- 20050630 LR - 20191210 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 1041 IP - 2 DP - 2005 Apr 18 TI - Effect of hypoxanthine on Na+,K+-ATPase activity and some parameters of oxidative stress in rat striatum. PG - 198-204 AB - The main objective of this study was to investigate the effects of preincubation of rat striatum homogenate in the presence of hypoxanthine, a metabolite accumulated in Lesch-Nyhan disease, on Na+,K+-ATPase activity and on some parameters of oxidative stress namely thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant parameter (TRAP) and membrane protein thiol content. Results showed that hypoxanthine significantly increased TBA-RS and reduced Na+,K+-ATPase activity, TRAP and membrane protein thiol content. In addition, we also evaluated the effect of glutathione, trolox, allopurinol and Nvarpi-nitro-L-arginine methyl ester (L-NAME) on the inhibitory effect of hypoxanthine on Na+,K+-ATPase activity in the same rat cerebral structure. All tested compounds per se did not alter Na+,K+-ATPase activity, but only glutathione and trolox prevented the effect of hypoxanthine on the enzyme activity. The effect of glutathione and trolox on hypoxanthine-induced increase of TBA-RS levels was also investigated. These antioxidants alone or combined with hypoxanthine reduced TBA-RS levels. Our present findings show that hypoxanthine induces oxidative stress in rat striatum and that the inhibition of Na+,K+-ATPase activity caused by this oxypurine was probably mediated by reactive oxygen species. It is presumed that these results might be associated with the neuronal dysfunction of patients affected by Lesch-Nyhan disease. FAU - Bavaresco, Caren Serra AU - Bavaresco CS AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil. FAU - Chiarani, Fabria AU - Chiarani F FAU - Matte, Cristiane AU - Matte C FAU - Wajner, Moacir AU - Wajner M FAU - Netto, Carlos Alexandre AU - Netto CA FAU - de Souza Wyse, Angela Terezinha AU - de Souza Wyse AT LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Antioxidants) RN - 0 (Enzyme Inhibitors) RN - 0 (Free Radicals) RN - 0 (Membrane Proteins) RN - 0 (Sulfhydryl Compounds) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 2TN51YD919 (Hypoxanthine) RN - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Corpus Striatum/*drug effects/enzymology/physiopathology MH - Enzyme Inhibitors/pharmacology MH - Free Radicals/metabolism MH - Hypoxanthine/*pharmacology MH - Lesch-Nyhan Syndrome/metabolism MH - Membrane Proteins/chemistry/drug effects/metabolism MH - Models, Neurological MH - Neurons/chemistry/*drug effects/enzymology MH - Oxidative Stress/*drug effects/physiology MH - Rats MH - Rats, Wistar MH - Sodium-Potassium-Exchanging ATPase/*drug effects/metabolism MH - Subcellular Fractions MH - Sulfhydryl Compounds/metabolism MH - Synaptic Membranes/drug effects/enzymology MH - Synaptic Transmission/drug effects/physiology MH - Thiobarbituric Acid Reactive Substances/metabolism EDAT- 2005/04/15 09:00 MHDA- 2005/07/01 09:00 CRDT- 2005/04/15 09:00 PHST- 2004/05/13 00:00 [received] PHST- 2005/02/01 00:00 [revised] PHST- 2005/02/04 00:00 [accepted] PHST- 2005/04/15 09:00 [pubmed] PHST- 2005/07/01 09:00 [medline] PHST- 2005/04/15 09:00 [entrez] AID - S0006-8993(05)00245-3 [pii] AID - 10.1016/j.brainres.2005.02.012 [doi] PST - ppublish SO - Brain Res. 2005 Apr 18;1041(2):198-204. doi: 10.1016/j.brainres.2005.02.012.