Protective effects of DL-alpha-lipoic acid on cadmium-induced deterioration of rat hepatocytes.
The suitability of DL-alpha-lipoic acid (LA) to serve as an antidote in cadmium (Cd) toxicity in rat hepatocytes was investigated. Isolated hepatocytes were exposed to 200 and 450 microM Cd in the presence of 0.2, 1.0 and 5.0 mM LA, respectively. After 30 min of incubation various criteria of cell viability were monitored. Lipoic acid markedly diminished Cd uptake. Concomitantly, Cd-induced membrane injury, as reflected by the leakage of aspartate aminotransferase and sorbitol dehydrogenase (SDH) was decreased. Moreover, LA protected against intracellular toxic responses to Cd, such as a decrease in cellular SDH activity, a decrease in cellular acid soluble thiols, especially in total glutathione, a decrease in cellular urea and an increase in thiobarbituric acid (TBA) reactants, as a measure of lipid peroxidation. Most protective effects were seen in hepatocytes challenged with the lower Cd concentration and coincubated with 5 mM LA. In contrast, at 450 microM Cd even the highest LA concentration applied either did only reverse Cd-effects incompletely (SDH-response, TBA-reactants) or did not protect at all (Cd uptake, enzyme leakage, loss of glutathione). The data indicate that DL-alpha-lipoic acid serves as a protective tool against Cd-induced membrane damage and cell dysfunction in hepatocytes. This stands as long as Cd exposure is low enough to permit interaction with LA prior to interaction with cell structures.
Müller
L
L
Institute of Toxicology, University of Düsseldorf, F.R.G.
D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D013385:Succinate Dehydrogenase / Q000032:analysis; D013438:Sulfhydryl Compounds / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D002104:Cadmium; D008063:Thioctic Acid; D013385:Succinate Dehydrogenase