α-硫辛酸和维生素C对慢性砷染毒大鼠氧化应激的保护作用

Effects of α-lipoic acid and vitamin C on oxidative stress in rat exposed to chronic arsenic toxicity

目的 探究α-硫辛酸（α-LA）和维生素C对慢性砷染毒大鼠氧化应激的保护作用.方法 50只雄性SD大鼠,随机分为空白对照组、饮水慢性砷染毒组（As组）、α-LA干预组、维生素C干预组、α-LA＋维生素C干预组.除空白对照组自由饮用去离子水6周外,其余4组均自由饮用含有50mg/L砷酸钠的饮用水6周;α-LA干预组同时灌胃α-LA 10mg·kg-1·d-1,维生素C干预组同时灌胃维生素C 25 mg·kg-1·-1,α-LA＋维生素C干预组同时灌胃α-LA 10 mg·k g-1·d-1和维生素C 25 mg·kg-1·d-1.6周后,各组动物由腹主动脉取血,并分别测定血液、脑和肝组织中δ-氨基-γ-酮戊酸脱水酶（δ-ALAD）、半胱天冬蛋白酶（Caspase-3）、ATPase、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）活力,测定还原型谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）、硫代巴比妥酸反应产物（TBARS）和活性氧（ROS）含量.结果 与对照组[ROS为（10260.72±525.28）U/ml,δ-ALAD为（19.78±2.27）nmol/ml]比较,As组血清中ROS含量[（14930.49±647.41）U/ml]明显增加,δ-ALAD活力[（6.45±0.73）nmol/ml]明显下降,差异均有统计学意义（P＜0.05,P＜0.01）;与As组比较,α-LA和维生素C干预组δ-ALAD活力[分别为（10.15±0.38）、（10.2 1±0.45）、（15.04±0.36）nmol/ml]明显增加,α-LA＋维生素C干预组ROS含量[（1 1305.20±568.58）U/ml]明显下降,差异均有统计学意义（P＜0.05,P＜0.01）.与对照组比较,As组脑和肝组织匀浆中ROS含量、Caspase-3活力、TBARS含量明显增加,而ATPase、SOD、GSH-Px和CAT活力均明显下降,差异均有统计学意义（P＜0.05）;与As组比较,α-LA和维生素C干预组脑组织中ROS含量均明显下降,α-LA＋维生素C干预组Caspase-3活力和TBARS含量明显下降,SOD、GSH-Px和CAT活力均明显增加,差异均有统计学意义（P＜0.05）.结论 α-LA和维生素C干预对慢性砷染毒大鼠氧化应激具有保护作用.膳食中合理地添加α-LA和维生素C对预防饮水砷毒性有重要作用.

Objective To explore arsenic-induced oxidative stress and the protective efficacy of α-lipoic acid and vitamin c.Methods 50 male SD rats were randomly divided into 5 groups.Ten rats（the control group）were exposed to deionized water for 6 weeks, and the others were alone exposed to sodium arsenite （50 mg/L water）for 6 weeks, at the same time, three group rats were administered intragastrically（I.g.）with α-lipoic acid 10 mg· kg-1· d-1 and vitamin C 25 mg· kg-1· d-1 either alone or in combination.At the end of experiment, blood was drawn from abdominal aorta, and then the blood, brain and liver of rats were used for biochemical assays, including blood glutathione（GSH）, δ-aminolevulinic acid dehydratase（δ-ALAD）, reactive oxygen species（ROS）and oxidized glutathione（GSSG）level.At the same time, the super oxide dismutase（SOD）activity, glutathione peroxidase（GSH-Px）activity, catalase（CAT）activity, ATPase activity of brain and liver were determined.The caspase activity of brain were also determined.Results There were a significant increase in ROS level（P＜0.05）, but a significant decrease in δ-ALAD activity（P＜0.01）in the chronic arsenic toxicity model group compared with the control group.These alterations were marginally restored by co-administration of vitamin C and α-lipoic acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite in rat（P＜0.05）.At the same time, there was a significant increase in the ROS and TBARS level of the brain and liver（P＜0.05）, and caspase activity of the brain（P＜0.05）, while there was a significant decrease in antioxidant enzymes and ATPase activity on arsenite exposure in rats（P＜0.05）.These alterations were also marginally restored by co-administration of vitamin C and α-lipoic acid individually, while significant recovery was observed in the animals supplemented with both the antioxidants together with arsenite in rat（P＜0.05）.Conclusions Arsenite-induced oxidative stress can be significantly protected by co-administration of o-lipoic acid and vitamin C individually, but the best effects could be observed with combined administration of two antioxidants during arsenite exposure in animals.The dietary intervention of or supplementation with natural dietary nutrients is possible to prevent the effects of arsenic in populations of risk.