Despite voluminous research, the cellular and molecular mechanism of heavy metal toxicity is yet to be understood. The proposed research plans to evaluate two current hypotheses to explain the mechanism of metal toxicity; that lipid peroxidation is an indicator of cell injury, and that heavy metals interact with Ca2+ binding sites of calmodulin. The specific objectives are: a) to determine the influence of zinc and selenium on the effects of mercury and cadmium on -SH enzymes and uptake of dopamine and norepinephrine, b) to determine the influence of age on metal toxicity, d) to study the effect of heavy metals on lipid peroxidation, e) to study the calmodulin influence on the metal toxicity, f) to develop a biomodel using various experimental data to explain the biomechanism of metal toxicity. We have proposed to use the rat brain synaptosomes and liver plasma membrane of male Sprague Dawley rats. For aging studies, Male Fisher-344 rats will be used. Cadmium, mercury and lead will be used. An important task of the proposed research is to train undergraduate students not only in biological research, but also in the application of computer in research. The objective will be achieved by detailed studies of metal toxicity on -SH enzyme, lipid peroxidation, calmodulin-effect, influence of age and computer applications. Protective effects of Zinc and selenium will also be included. An effort will be made to build a biomodel with all the research parameters to show how each research information can be interrelated with the other, and this might provide an explanation for the biomechanism of heavy metal toxicity. The proposed research involves three undergraduate students at all phases of research and computation work. The proposed research is expected to provide new insights in our understanding of the mechanisms involved in heavy metal toxicity.
