Bludovská M, Kotyzová D, Koutenský J, Eybl V
Department of Pharmacology and Toxicology, Charles University, Faculty of Medicine, Pilsen, Czech Republic.
Gen Physiol Biophys. 1999 Oct;18 Spec No:28-32.
Alpha-lipoic acid (alpha-LA) is an important antioxidant drug with chelating properties. In experiments performed in male mice (CD-1, Charles River) the effects of cadmium on lipid peroxidation (LP), GSH level, the activity of catalase and glutathione peroxidase (GSH-Px) in liver homogenates were studied. Mice were injected with CdCl2 x 2.5 H2O at a dose of 40 micromol x kg(-1) s.c. Alpha-LA was administered simultaneously i.p. at the dose corresponding to alpha-LA-to-Cd molar ratio of 5:1. The experiments were completed at 24 h. Cadmium increased LP to 200.7% of controls. This effect was prevented by alpha-LA treatment (p < or = 0.05). GSH level was decreased to 81.7% of controls and it was not affected by alpha-LA. GSH-Px activity diminished by Cd administration was corrected by alpha-LA (p < 0.001). Catalase activity decreased by Cd remained unaffected. The administration of alpha-LA alone enhanced LP and the activity of catalase. As estimated by AAS, Cd content in the liver, the kidneys, the brain and the testes remained unaffected by alpha-LA treatment. In the acute toxicity experiment, the mortality associated with cadmium was decreased by alpha-LA administration. The results suggest that the toxicity of Cd was decreased mainly by the antioxidant activity of alpha-LA rather than by cadmium removal from tissues.
α-硫辛酸(α-LA)是一种具有螯合特性的重要抗氧化药物。在对雄性小鼠(CD-1,查尔斯河实验室)进行的实验中,研究了镉对肝脏匀浆中脂质过氧化(LP)、谷胱甘肽(GSH)水平、过氧化氢酶和谷胱甘肽过氧化物酶(GSH-Px)活性的影响。小鼠皮下注射剂量为40微摩尔/千克的CdCl₂·2.5H₂O。同时腹腔注射α-LA,其剂量对应α-LA与镉的摩尔比为5:1。实验在24小时后完成。镉使LP增加至对照组的200.7%。α-LA处理可防止这种效应(p≤0.05)。GSH水平降至对照组的81.7%,且不受α-LA影响。镉给药导致的GSH-Px活性降低被α-LA纠正(p<0.001)。镉导致的过氧化氢酶活性降低未受影响。单独给予α-LA可增强LP和过氧化氢酶活性。通过原子吸收光谱法估计,肝脏、肾脏、大脑和睾丸中的镉含量不受α-LA处理的影响。在急性毒性实验中,α-LA给药降低了与镉相关的死亡率。结果表明,镉的毒性降低主要是由于α-LA的抗氧化活性,而非通过从组织中去除镉。