Leeuwenburgh C, Ji L L
Department of Kinesiology, Interdepartmental Graduate Program of Nutritional Sciences, University of Wisconsin-Madison, WI 53706, USA.
J Nutr. 1998 Dec;128(12):2420-6. doi: 10.1093/jn/128.12.2420.
The present study examined the effect of glutathione (GSH) and glutathione ethyl ester (GSH-E) supplementation on GSH homeostasis and exercise-induced oxidative stress. Male Swiss-Webster mice were randomly divided into 4 groups: starved for 24 h and injected with GSH or GSH-E (6 mmol/kg body wt, i.p.) 1 h before exercise, starved for 24 h and injected with saline (S); and having free access to food and injected with saline (C). Half of each group of mice was killed either after an acute bout of exhaustive swimming (E) or after rest (R). Plasma GSH concentration was 100-160% (P < 0.05) higher in GSH mice vs. C or S mice at rest, whereas GSH-E injection had no effect. Plasma GSH was not affected by exercise in C or S mice, but was 44 and 34% lower (P < 0.05) in E vs. R mice with GSH or GSH-E injection, respectively. S, GSH- and GSH-E-treated mice had significantly lower liver GSH concentration and the GSH:glutathione disulfide (GSSG) ratio than C mice. Hepatic and renal GSH and the GSH:GSSG ratio were significantly lower in E vs. R mice in all groups. GSH-E-treated mice had a significantly smaller exercise-induced decrease in GSH vs. C, S, and GSH-treated mice and no difference in the GSH:GSSG ratio in the kidney. Activities of gamma-glutamylcysteine synthetase and gamma-glutamyltranspeptidase in the liver and kidney were not affected by either GSH treatment or exercise. GSH concentration and the GSH:GSSG ratio in quadriceps muscle were not different among C, S and GSH-treated mice, but significantly lower in GSH-E-treated mice (P < 0.05). Hepatic malondialdehyde (MDA) content was greater in exercised mice in all but GSH-E-treated groups. GSH and GSH-E increased MDA levels in the kidney of E vs. R mice, but attenuated exercise-induced lipid peroxidation in muscle. Swim endurance time was approximately 2 h longer in GSH (351 +/- 22 min) and GSH-E (348 +/- 27) than S mice (237 +/- 17). We conclude that 1) acute GSH and GSH-E supplementation at the given doses does not increase tissue GSH content or redox status; 2) both GSH and GSH-E improve endurance performance and prevent muscle lipid peroxidation during prolonged exercise; and 3) while both compounds may impose a metabolic and oxidative stress to the kidney, this side effect is smaller with GSH-E supplementation.
本研究考察了补充谷胱甘肽（GSH）和谷胱甘肽乙酯（GSH-E）对GSH内稳态及运动诱导的氧化应激的影响。雄性瑞士-韦伯斯特小鼠被随机分为4组：饥饿24小时，并在运动前1小时腹腔注射GSH或GSH-E（6 mmol/kg体重）；饥饿24小时，并注射生理盐水（S）；自由进食并注射生理盐水（C）。每组小鼠的一半在急性力竭游泳（E）后或休息（R）后处死。静息时，GSH组小鼠的血浆GSH浓度比C组或S组小鼠高100%-160%（P<0.05），而注射GSH-E则无此效果。C组或S组小鼠的血浆GSH不受运动影响，但在注射GSH或GSH-E的小鼠中，E组小鼠的血浆GSH分别比R组小鼠低44%和34%（P<0.05）。S组、GSH组和GSH-E组处理的小鼠肝脏GSH浓度及GSH:氧化型谷胱甘肽（GSSG）比值显著低于C组小鼠。所有组中，E组小鼠肝脏和肾脏的GSH及GSH:GSSG比值均显著低于R组小鼠。与C组、S组和GSH组处理的小鼠相比，GSH-E组处理的小鼠运动诱导的GSH降低幅度显著更小，且肾脏中GSH:GSSG比值无差异。肝脏和肾脏中γ-谷氨酰半胱氨酸合成酶及γ-谷氨酰转肽酶的活性不受GSH处理或运动的影响。C组、S组和GSH组处理的小鼠股四头肌中的GSH浓度及GSH:GSSG比值无差异，但GSH-E组处理的小鼠中该比值显著更低（P<0.05）。除GSH-E组处理的组外，所有运动小鼠的肝脏丙二醛（MDA）含量均更高。在E组与R组小鼠中，GSH和GSH-E增加了肾脏中的MDA水平，但减轻了运动诱导的肌肉脂质过氧化。GSH组（351±22分钟）和GSH-E组（348±27分钟）的游泳耐力时间比S组小鼠（237±17分钟）长约2小时。我们得出结论：1）以给定剂量急性补充GSH和GSH-E不会增加组织GSH含量或氧化还原状态；2）GSH和GSH-E均能提高耐力表现，并在长时间运动期间预防肌肉脂质过氧化；3）虽然这两种化合物可能对肾脏施加代谢和氧化应激，但补充GSH-E时这种副作用更小。
