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 c ompounds has been suggested to protect against the toxic effects of re duced oxygen species by contributing to the thiol pool of the cell. Th e present study was designed to determine whether dietary supplementat ion of DL alpha-lipoic acid (15 and 30 mg/kg), a ''meta-vitamin,'' to cadmium-intoxicated vats (3 mg/kg) affords protection against the oxid ative stress caused by the metal. The fiver and kidney of the metal-ad ministered rats showed elevated levels of hydroxyl radicals and malond ialdehyde (basal and induced), a decreased level of antioxidants-reduc ed glutathione, total thiols protein thiols, nonprotein thiols, ascorb ate, alpha-tocopherol and retinol and antioxidizing enzymes-superoxide dismutase, catalase, tau-glutamyl transpeptidase, glutathione peroxid ase, glucose-6-phosphate dehydrogenase, glutathione reductase, and glu tathione-S-transferase. Lipoate supplementation changed the tissue red ox state directly by scavenging the free radicals and indirectly by bo lstering the antioxidants and antioxidizing enzyme defenses. In vitro studies revealed that, among the mono and dithiols (glutathione, cyste ine, dithiothreitol, and lipoic acid), lipoic acid was the most potent scavenger of free radicals produced during cadmium-induced hepatotoxi city. The drug contributes its thiol groups to detoxify the divalent m etal and subsequently ameliorates the cell membrane integrity.