Reversal of lead-induced oxidative stress by chelating agent, antioxidant, or their combination in the rat.
The influence of N-acetyl cysteine (NAC), an antioxidant, on the therapeutic efficacy of meso-2,3-dimercaptosuccinic acid (DMSA), a hydrophilic, and its ester, monoisoamyl 2,3-dimercaptosuccinate (MiADMS), a lipophilic, both soft tissue lead mobilizers, was investigated in lead-preexposed rats. The subsequent treatment of lead-exposed animals with DMSA, MiADMS, or NAC reversed the lead-induced alterations in blood delta-aminolevulinic acid dehydratase, catalase, malondialdehyde (MDA), reduced glutathione, oxidized glutathione, and brain MDA levels. The combined treatment with DMSA and NAC was more effective than that with MiADMS and NAC in enhancing the restoration of all these parameters indicative of lead-induced oxidative stress. These reversals were consistent with the lead-removing ability of DMSA and MiADMS but not that of NAC. As the reversal of these parameters by NAC was independent of its lead-mobilizing capability, this ought to be mainly due to its strong antioxidant property. The increase in blood and brain zinc levels upon lead exposure appears to be the result of the redistribution of endogenous zinc due to lead. Subsequent treatment with DMSA, MiADMS, NAC, or their combination decreased the brain zinc as its excretable complexes with a transient increase in blood zinc level. The ideal treatment of lead poisoning seems to be a combination of a lead chelator and an antioxidant.
D000111:Acetylcysteine / Q000494:pharmacology*; D000622:Aminolevulinic Acid / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D002374:Catalase / Q000097:blood; D002614:Chelating Agents / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000097:blood; D007668:Kidney / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D007855:Lead Poisoning / Q000188:drug therapy; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D004113:Succimer / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000975:Antioxidants; D002614:Chelating Agents; D016166:Free Radical Scavengers; D007854:Lead; D008315:Malondialdehyde; D000622:Aminolevulinic Acid; C091888:monoisoamyl-2,3-dimercaptosuccinate; D004113:Succimer; D002374:Catalase; D005978:Glutathione; D000111:Acetylcysteine