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. The 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 rats 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, administration of LA after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of LA to cultures of CHO cells significantly increased cell survival, that was inhibited by lead treatment in a concentration-dependent manner. Administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Hence, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent.
Gurer
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H
Department of Chemistry, University of Missouri-Rolla, 65409-0010, USA.
Ozgunes
H
H
Oztezcan
S
S
Ercal
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N
D000818:Animals; D000975:Antioxidants; D016466:CHO Cells; D002374:Catalase / Q000378:metabolism; D006224:Cricetinae; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007854:Lead / Q000378:metabolism; D007855:Lead Poisoning; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D008063:Thioctic Acid / Q000008:administration & dosage / Q000502:physiology*
D000975:Antioxidants; D007854:Lead; D008315:Malondialdehyde; D008063:Thioctic Acid; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005978:Glutathione