The influence of alpha-lipoic acid on the toxicity of cadmium.
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.
Bludovská
M
M
Department of Pharmacology and Toxicology, Charles University, Faculty of Medicine, Pilsen, Czech Republic. bludovsk@lfp.cuni.cz
Kotyzová
D
D
Koutenský
J
J
Eybl
V
V
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002104:Cadmium / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D014018:Tissue Distribution
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D002104:Cadmium; D008315:Malondialdehyde; D008063:Thioctic Acid; D005979:Glutathione Peroxidase; D005978:Glutathione