阿斯巴甜对小鼠大脑记忆和氧化应激影响的研究。

Studies on the effects of aspartame on memory and oxidative stress in brain of mice.

机构信息

Department of Toxicology and Narcotics, National Research Centre, Cairo, Egypt.

出版信息

Eur Rev Med Pharmacol Sci. 2012 Dec;16(15):2092-101.

Abstract

OBJECTIVE

The dipeptide aspartame (N-L-alpha-aspartyl-Lphenylalanine, 1-methyl ester; alpha-APM) is one of the most widely used artificial sweeteners. The present study aimed to investigate the effect of repeated administration of aspartame in the working memory version of Morris water maze test, on oxidative stress and brain monoamines in brain of mice.

MATERIALS AND METHODS

Aspartame (0.625, 1.875 or 5.625 mg/kg) was administered once daily subcutaneously for 2 weeks and mice were examined four times a week for their ability to locate a submerged plate. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide levels (the concentrations of nitrite/nitrate) and glucose were determined in brain.

RESULTS

Only at the highest dose of 5.625 mg/kg, did aspartame significantly impaired water maze performance. The mean time taken to find the escape platform (latency) over 2 weeks was significantly delayed by aspartame 5.625 mg/kg, compared with the saline-treated control group. Significant differences occurred only on the first trial to find the escape platform. Significant increase in brain MDA by 16.5% and nitric oxide by 16.2% and a decrease in GSH by 25.1% and glucose by 22.5% occurred after treatment with aspartame at 1.875 mg/kg. Aspartame administered at 5.625 mg/kg significantly increased brain MDA by 43.8%, nitric oxide by 18.6% and decreased GSH by 32.7% and glucose by 25.8%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline and dopamine.

CONCLUSIONS

These findings suggest impaired memory performance and increased brain oxidative stress by repeated aspartame administration. The impaired memory performance is likely to involve increased oxidative stress as well as decreased brain glucose availability.

摘要

目的

二肽甜味剂阿斯巴甜（N-L-α-天冬氨酰-L-苯丙氨酸 1-甲酯；α-APM）是使用最广泛的人工甜味剂之一。本研究旨在探讨重复给予阿斯巴甜对小鼠水迷宫工作记忆测试中氧化应激和脑单胺的影响。

材料和方法

阿斯巴甜（0.625、1.875 或 5.625mg/kg）每天皮下给药一次，持续 2 周，每周四次检查小鼠寻找下沉板的能力。测定脑内丙二醛（MDA）、还原型谷胱甘肽（GSH）、一氧化氮水平（亚硝酸盐/硝酸盐浓度）和葡萄糖。

结果

只有在最高剂量 5.625mg/kg 时，阿斯巴甜才显著损害水迷宫表现。与生理盐水处理的对照组相比，阿斯巴甜 5.625mg/kg 组在 2 周内找到逃生平台（潜伏期）的平均时间明显延迟。仅在第一次寻找逃生平台的试验中出现显著差异。用 1.875mg/kg 的阿斯巴甜处理后，脑 MDA 增加 16.5%，一氧化氮增加 16.2%，GSH 减少 25.1%，葡萄糖减少 22.5%。用 5.625mg/kg 的阿斯巴甜处理后，脑 MDA 增加 43.8%，一氧化氮增加 18.6%，GSH 减少 32.7%，葡萄糖减少 25.8%。阿斯巴甜呈剂量依赖性抑制脑内 5-羟色胺、去甲肾上腺素和多巴胺。