Antioxidant role of alpha-lipoic acid in lead toxicity

The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. Th e present study was designed to investigate the efficacy of lipoic acid (LA ) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, LA's ability to decrease lead levels in the blood and tissues of lead-treated ra ts was examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, ad ministration of LA after lead treatment significantly decreased catalase an d red blood cell glucose-6-phosphate dehydrogenase activity. In vitro admin istration of LA to cultures of CHO cells significantly increased cell survi val, that was inhibited by lead treatment in a concentration-dependent mann er. Administration of LA was not effective in decreasing blood or tissue le ad levels compared to a well-known chelator, succimer, that was able to red uce them to control levels. Hence, LA seems to be a good candidate for ther apeutic intervention of lead poisoning, in combination with a chelator, rat her than as a sole agent. (C) 1999 Elsevier Science Inc.