Despite the fact that 3 million children are affected by lead poisoning, efforts to treat these children and to eliminate lead from the environment have been inadequate. At present, the only approved clinical intervention method is chelation with calcium disodium ethylenediaminetetraacetic acid (CaNaEDTA), D-penicillamine, and British Anti-Lewisite. CaNaEDTA in particular, is widely used despite its high cost ($30,000 per child) and severe side effects. The most undesirable effects observed during CaNaEDTA treatment were the increased urinary excretion of zinc and iron, and the redistribution of lead from its innocuous bone site to crucial soft tissues such as the brain. For these reasons, most physicians prefer not to treat children with lead levels of less than 45 ug/dL. In addition to other toxicities, lead has been shown to induce oxidative stress both in vivo and in vitro. Our previous studies demonstrated that treatment with N-acetylcysteine (NAC) seemed to improve oxidative stress parameters and it also showed some chelating action in lead-exposed animals. These data suggest that antioxidants may play an important role as therapeutic agents in lead poisoning. We speculate that an effective long-term therapy for lead poisoning must encompass both a chelating agent and antioxidant administration. The proposed work will explore the use of the natural antioxidants alpha-lipoic acid, taurine, alpha-tocopherol (vitamin E), and ascorbic acid (vitamin C) in treatment of lead poisoning. At least three important benefits will be derived from the proposed study: 1. The role of oxidative stress in lead toxicity will be clarified; 2. The benefits of various antioxidants in subclinical lead intoxication (blood lead less than 45 ug/dL) will be examined; 3. The adjunctive use of antioxidants with a new oral chelator succimer will be explored in clinical lead intoxication (blood lead greater than 45 ug/dL). Eventually we hope to provide evidence that the use of antioxidants will offer safe and effective treatment for a segment of the human population (children with moderate blood-lead levels) presently left untreated.
| Penugonda, Suman; Ercal, Nuran (2011) Comparative evaluation of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) on glutamate and lead-induced toxicity in CD-1 mice. Toxicol Lett 201:1-7 |
| Gurer, H; Ozgunes, H; Oztezcan, S et al. (1999) Antioxidant role of alpha-lipoic acid in lead toxicity. Free Radic Biol Med 27:75-81 |
| Yusof, M; Yildiz, D; Ercal, N (1999) N-acetyl-L-cysteine protects against delta-aminolevulinic acid-induced 8-hydroxydeoxyguanosine formation. Toxicol Lett 106:41-7 |
