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急性给予 5-氧脯氨酸会导致幼鼠大脑皮质和小脑的脂质和蛋白质氧化损伤,并损害抗氧化防御系统。

Acute administration of 5-oxoproline induces oxidative damage to lipids and proteins and impairs antioxidant defenses in cerebral cortex and cerebellum of young rats.

机构信息

Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, Porto Alegre, RS, Brazil.

出版信息

Metab Brain Dis. 2010 Jun;25(2):145-54. doi: 10.1007/s11011-010-9190-1. Epub 2010 Apr 30.

Abstract

5-Oxoproline accumulates in glutathione synthetase deficiency, an autossomic recessive inherited disorder clinically characterized by hemolytic anemia, metabolic acidosis, and severe neurological symptoms whose mechanisms are poorly known. In the present study we investigated the effects of acute subcutaneous administration of 5-oxoproline to verify whether oxidative stress is elicited by this metabolite in vivo in cerebral cortex and cerebellum of 14-day-old rats. Our results showed that the acute administration of 5-oxoproline is able to promote both lipid and protein oxidation, to impair brain antioxidant defenses, to alter SH/SS ratio and to enhance hydrogen peroxide content, thus promoting oxidative stress in vivo, a mechanism that may be involved in the neuropathology of gluthatione synthetase deficiency.

摘要

5-氧脯氨酸在谷胱甘肽合成酶缺乏症中积累,这是一种常染色体隐性遗传性疾病,临床上表现为溶血性贫血、代谢性酸中毒和严重的神经症状,但其发病机制尚不清楚。在本研究中,我们研究了急性皮下给予 5-氧脯氨酸对 14 日龄大鼠大脑皮质和小脑氧化应激的影响,以验证这种代谢物是否在体内引发氧化应激。结果表明,急性给予 5-氧脯氨酸能够促进脂质和蛋白质氧化,损害大脑抗氧化防御,改变 SH/SS 比值并增加过氧化氢含量,从而在体内引发氧化应激,这一机制可能与谷胱甘肽合成酶缺乏症的神经病理学有关。

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