Latini Alexandra, Borba Rosa Rafael, Scussiato Karina, Llesuy Susana, Belló-Klein Adriane, Wajner Moacir
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Río Grande do Sul, Porto Alegre, RS, Brazil.
Brain Res. 2002 Nov 29;956(2):367-73. doi: 10.1016/s0006-8993(02)03573-4.
Glutaryl-CoA dehydrogenase deficiency (GDD) is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of glutaric, 3-hydroxyglutaric (3-OHGA) and glutaconic acids and clinically by severe neurological symptoms and cerebral atrophy whose pathophysiology is poorly known. In the present study we investigated the effect of 3-OHGA, considered the main neurotoxin in GDD, on the lipoperoxidation parameters chemiluminescence and thiobarbituric acid-reactive species (TBA-RS), and on the amount of nitric oxide metabolites in cerebral cortex of young rats. Total radical-trapping antioxidant potential (TRAP), which reflects the tissue antioxidant defenses, was also examined. We observed that 3-OHGA significantly increased chemiluminescence, TBA-RS and nitric oxide metabolites, in contrast to TRAP, which was decreased by the metabolite. The data indicate a stimulation of lipid peroxidation and free radical production, and a reduction of the tissue antioxidant defenses caused by the metabolite. In case these findings also occur in the human condition, it may be presumed that oxidative stress is involved in the brain damage observed in GDD.
戊二酰辅酶A脱氢酶缺乏症（GDD）是一种遗传性神经代谢紊乱疾病，其生化特征是组织中戊二酸、3-羟基戊二酸（3-OHGA）和戊烯二酸蓄积，临床特征为严重的神经症状和脑萎缩，其病理生理学尚不清楚。在本研究中，我们研究了被认为是GDD主要神经毒素的3-OHGA对幼鼠大脑皮质脂质过氧化参数化学发光和硫代巴比妥酸反应性物质（TBA-RS）以及一氧化氮代谢产物量的影响。还检测了反映组织抗氧化防御能力的总自由基捕获抗氧化能力（TRAP）。我们观察到，与TRAP相反，3-OHGA显著增加了化学发光、TBA-RS和一氧化氮代谢产物，而TRAP则被该代谢产物降低。数据表明该代谢产物刺激了脂质过氧化和自由基产生，并降低了组织抗氧化防御能力。如果这些发现也出现在人类身上，可以推测氧化应激与GDD中观察到的脑损伤有关。
