Role of Selenocystine in Lead Toxicity

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DESCRIPTION (provided by applicant): Despite several efforts to reduce lead levels in the environment, lead exposure continues to be a major public health problem, particularly in urban areas in the US, as well as in third world countries. Lead can enter biological systems via food, water, air and soil. In 1978, lead-based paint was banned. Despite this ban, it was reported that 38 million living units in the US alone still contained lead-based paint in 2002. Drinking water can become contaminated by lead. Municipal infrastructure distribution systems contain lead or copper service pipes (joined by a lead solder). A recent survey (2004) estimates that 18% households in the DC area have lead service pipes and 30% of the tested people have blood lead levels greater than 5 mg/dL. Conventional treatment of lead poisoning is to use chelators that bind to lead. Unfortunately, presently available chelators have severe side effects therefore many physicians prefer not to use them. Lead poisoning is not the only disorder chelators are used, other disorders include heavy metal toxicities (mercury and cadmium toxicity), autism (in the belief that heavy metal toxicity might be the cause) and coronary artery disease (in the belief that chelators eliminate calcified atherosclerotic plaques). Recent case reports (2005) also indicated that health-care providers who are unfamiliar with chelating agents used Na2EDTA instead CaNa2EDTA to eliminate lead in children. This was a fatal mistake because Na2EDTA induces hypocalcemia and possibly fatal tetany. Therefore, use of chelators like CaNa2EDTA in lead poisoning can be very harmful and it is very costly ($30,000 per child). Because lead induces free radicals indirectly, our previous studies with natural antioxidants showed insignifivant chelation action for lead. Recently, a newly designed amide form of N-acetyl cysteine (Nacetylcysteine amide, NACA) showed promising antioxidant/chelation effects. Binding characteristics of this antioxidant and previously tested ones along with known-chelators have not been investigated. Therefore, this continuation of our NIH (2R15ES 09497-02) proposal will primarily explore: 1) the dual benefits of NACA, both as a chelator and as an antioxidant, and 2) binding constants of chelators and antioxidants.