Effect of DL alpha-lipoic acid on tissue redox state in acute cadmium-challenged tissues

Cadmium as an environmental pollutant has aroused great concern due to its toxic effects on various body tissues. Supplementation of thiol compounds has been suggested to protect against the toxic effects of reduced oxygen species by contributing to the thiol pool of the cell. The present study was designed to determine whether dietary supplementation of DL alpha-lipoic acid (15 and 30 mg/kg), a ''meta-vitamin,'' to cadmium-intoxicated vats (3 mg/kg) affords protection against the oxidative stress caused by the metal. The fiver and kidney of the metal-administered rats showed elevated levels of hydroxyl radicals and malondialdehyde (basal and induced), a decreased level of antioxidants-reduced glutathione, total thiols protein thiols, nonprotein thiols, ascorbate, alpha-tocopherol and retinol and antioxidizing enzymes-superoxide dismutase, catalase, tau-glutamyl transpeptidase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, glutathione reductase, and glutathione-S-transferase. Lipoate supplementation changed the tissue redox state directly by scavenging the free radicals and indirectly by bolstering the antioxidants and antioxidizing enzyme defenses. In vitro studies revealed that, among the mono and dithiols (glutathione, cysteine, dithiothreitol, and lipoic acid), lipoic acid was the most potent scavenger of free radicals produced during cadmium-induced hepatotoxicity. The drug contributes its thiol groups to detoxify the divalent metal and subsequently ameliorates the cell membrane integrity.