Tansini C M, Durigon K, Testa C G, Belló-Klein A, Wajner M, Wannmacher C M D, Wyse A T S, Dutra-Filho C S
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, 90035-003 Porto Alegre, RS, Brazil.
Int J Dev Neurosci. 2004 Apr;22(2):67-72. doi: 10.1016/j.ijdevneu.2003.12.006.
Histidinemia is an inherited metabolic disorder caused by deficiency of histidase activity, which leads to tissue accumulation of histidine and its derivatives. Affected patients usually present with speech delay and mental retardation, although asymptomatic patients have been reported. Considering that the pathophysiology of the neurological dysfunction of histidinemia is not yet understood and since histidine has been considered a pro-oxidant agent, in the present study we investigated the effect of histidine and one of its derivatives, l-beta-imidazolelactic acid, at concentrations ranging from 0.1 to 10 mM, on various parameters of oxidative stress in cerebral cortex of 30-day-old Wistar rats. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), thiobarbituric acid reactive substances (TBA-RS), and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in tissue homogenates in the presence of l-histidine or l-beta-imidazolelactic acid. We observed that l-histidine provoked an increase of chemiluminescence and a reduction of TRAP at concentrations of 2.5 mM and higher, while TBA-RS measurement, GSH-Px, CAT and SOD activities were not affected. Furthermore, l-beta-imidazolelactic acid provoked antioxidant effects at high concentrations (5-10 mM) as observed by the reduction of chemiluminescence, although this compound enhanced chemiluminescence at low concentrations (0.5-1 mM). These results suggest that in vitro oxidative stress is elicited by histidine but only at supraphysiological concentrations.
组氨酸血症是一种遗传性代谢紊乱疾病，由组氨酸酶活性缺乏引起，导致组氨酸及其衍生物在组织中蓄积。尽管有报道称存在无症状患者，但受影响的患者通常表现为言语发育迟缓及智力障碍。鉴于组氨酸血症神经功能障碍的病理生理学尚未明确，且由于组氨酸被认为是一种促氧化剂，在本研究中，我们研究了组氨酸及其衍生物之一L-β-咪唑乳酸在0.1至10 mM浓度范围内，对30日龄Wistar大鼠大脑皮质氧化应激各项参数的影响。在存在L-组氨酸或L-β-咪唑乳酸的情况下，测定组织匀浆中的化学发光、总自由基捕获抗氧化能力（TRAP）、硫代巴比妥酸反应性物质（TBA-RS）以及抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性。我们观察到，L-组氨酸在浓度为2.5 mM及更高时会引起化学发光增加和TRAP降低，而TBA-RS测定、GSH-Px、CAT和SOD活性未受影响。此外，L-β-咪唑乳酸在高浓度（5 - 10 mM）时可产生抗氧化作用，表现为化学发光降低，尽管该化合物在低浓度（0.5 - 1 mM）时会增强化学发光。这些结果表明，体外氧化应激仅在超生理浓度下由组氨酸引发。
