Role of Selenocystine in Lead Toxicity

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DESCRIPTION (provided by applicant): Despite the fact that 3 million children are affected by lead poisoning each year in the United States, efforts to treat these children and to eliminate lead from the environment have been inadequate. Although chelating agents are currently available for the treatment of lead poisoning, they have severe side effects. Lead poisoning is considered a multifaceted problem since disruption of a variety of biochemical processes is responsible for toxicity rather than a single mechanism. Even though oxidative stress appears to play a major role, the molecular mechanisms of lead toxicity are not completely known. Our previous studies demonstrated that treatment with natural thiols (N-acetylcysteine, lipoic acid and taurine) significantly reversed lead-induced alterations in oxidative stress parameters, both in in vivo and in vitro models. However, none of these antioxidants showed any significant chelating action for lead. In our search for potential chelators and antioxidants for the treatment of lead poisoning, selenocystine (SeCys) gained our attention as a good candidate because its metabolic products are thiol-containing compounds known to be strong heavy metal chelators. Our preliminary results proved that SeCys is not only an effective antioxidant but it is also a good chelator. It significantly reduced blood lead levels (more than 50%), tissue lead levels (brain tissue was completely lead free after SeCYs treatment) and improved lead-induced oxidative stress, with no obvious side effects. Moreover, neurotoxic effects of lead were significantly diminished by SeCys by using a neuronal cell model (PC-12 cells). Therefore, this continuation of our NIH (2R15ES 09497-02) proposal will primarily explore: 1) chelating action of SeCys, 2) antioxidant role of SeCys, and 3) role of SeCys in reversing the neurotoxic effects of lead in lead poisoning.