Bavaresco Caren Serra, Chiarani Fabria, Wannmacher Clovis Milton Duval, Netto Carlos Alexandre, Wyse Angela Terezinha de Souza
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Metab Brain Dis. 2007 Mar;22(1):1-11. doi: 10.1007/s11011-006-9037-y. Epub 2007 Jan 17.
The main objective of this study was to investigate the effects of a single intrastriatal injection of hypoxanthine, a metabolite accumulated in Lesch Nyhan disease and possibly involved in its neuropathology, on Na(+),K(+)-ATPase activity, as well as on some parameters of oxidative stress, namely chemiluminescence (an index of lipid peroxidation), total radical-trapping antioxidant parameter--TRAP (an index of total antioxidant capacity of the tissue) and total thiol protein membrane content, in striatum, cerebral cortex and hippocampus of rats. Results show that hypoxanthine significantly decreased Na(+),K(+)-ATPase activity and TRAP while increased chemiluminescence in all ipsislateral structures tested. However, no effect on total thiol protein membrane content was detected. We suggest that hypoxanthine induces oxidative stress in all cerebral structures studied (striatum, hippocampus and cerebral cortex) and that the reduction of Na(+),K(+)-ATPase activity was probably mediated by reactive oxygen species.
本研究的主要目的是调查单次纹状体内注射次黄嘌呤(一种在莱施-奈恩病中积累且可能参与其神经病理学的代谢产物)对大鼠纹状体、大脑皮层和海马体中Na(+)、K(+)-ATP酶活性以及氧化应激的一些参数(即化学发光,脂质过氧化的指标;总自由基捕获抗氧化参数——TRAP,组织总抗氧化能力的指标;以及总硫醇蛋白膜含量)的影响。结果显示,次黄嘌呤显著降低了所有测试的同侧结构中的Na(+)、K(+)-ATP酶活性和TRAP,同时增加了化学发光。然而,未检测到对总硫醇蛋白膜含量有影响。我们认为,次黄嘌呤在所有研究的脑结构(纹状体、海马体和大脑皮层)中诱导氧化应激,并且Na(+)、K(+)-ATP酶活性的降低可能是由活性氧介导的。