Abstract:
Several degenerative pathologies mediated by oxidative stress have been linked to the altered activities of purine-dependent enzymes that participate in a number of signaling pathways. However, there is a dearth of information describing the possible involvement of dysfunctions in purinergic signaling system in Huntington diseases (HD) and thus still largely open a need to explore into this. In the present study, the influence of Fe2+-mediated increasing oxidative stress and thiol compounds on the activities of the purinergic enzymes (5’-nucleotidase (5’NT) and nucleoside triphosphate diphosphohydrolase (NTPDase)) were evaluated in vitro. In addition, HD-like symptoms were induced in rats by the administration of 3-nitropropionic acid (3NPA) via oral, intraperitoneal and subcutaneous routes and the redox status and activities of the purinergic enzymes were evaluated in the rat brain. The results revealed that under in vitro situation, Fe2+-mediated oxidative stress markedly inhibited the activities of both purinergic enzymes (5’NT and NTPDase) and this effect was prevented by the thiols. Also, irrespective of the HD model, there was a marked diminution in the redox status of the HD rats as typified by reduced level of reduced glutathione, decreased radical scavenging ability of the whole brain and elevated level of the lipid peroxidation product, malondialdehyde. Furthermore, the activities of the purinergic enzymes (5’NT and NTPDase) were profoundly increased and this effect was associated with concomitant decrease in the activities of cerebral sodium pump and delta-aminolevulinic acid dehydratase. Apparently, it appears that the pathophysiology of HD is multifactorial and likely involves dysfunctions in a number of molecular and biochemical events. Summarily, it is rational to speculate within the limit of the present data that potential therapeutic drugs in HD management will possibly target the redox systems as well as signaling systems linked with the purine-dependent enzymes in HD patients.
