Reactive intermediates are implicated in many disease processes, including amyotrophic lateral sclerosis, Alzheimer disease, ischemia reperfusion injury, as well as in drug toxicity. The reactive intermediates can include free radicals such as superoxide anion and nitric oxide as well as organic radicals derived from xenobiotics, including environmental pollutants and pharmacological agents. Many of these reactive metabolites have been found to react with hemoproteins due to their avidity to perform one-electron transfer reactions. We believe that such interactions may play a role in regulation of cellular processes but that inappropriate regulation may lead to toxicity or disease. We have focused on three specific areas of interest: the xenobiotic mediated regulation of nitric oxide synthase, a hemoprotein responsible for generation of nitric oxide from L-arginine, the oxidant- mediated regulation of various hemoproteins and the role of nitric oxide and reactive oxygen intermediates in apoptosis of T cells and in tissue toxicities.
