Review article
Oxidative mechanisms in the toxicity of metal ions

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Abstract

The role of reactive oxygen species, with the subsequent oxidative deterioration of biological macromolecules in the toxicities associated with transition metal ions, is reviewed. Recent studies have shown that metals, including iron, copper, chromium, and vanadium undergo redox cycling, while cadmium, mercury, and nickel, as well as lead, deplete glutathione and protein-bound sulfhydryl groups, resulting in the production of reactive oxygen species as superoxide ion, hydrogen peroxide, and hydroxyl radical. As a consequence, enhanced lipid peroxidation, DNA damage, and altered calcium and sulfhydryl homeostasis occur. Fenton-like reactions may be commonly associated with most membranous fractions including mitochondria, microsomes, and peroxisomes. Phagocytic cells may be another important source of reactive oxygen species in response to metal ions. Furthermore, various studies have suggested that the ability to generate reactive oxygen species by redox cycling quinones and related compounds may require metal ions. Recent studies have suggested that metal ions may enhance the production of tumor necrosis factor alpha (TNFα) and activate protein kinase C, as well as induce the production of stress proteins. Thus, some mechanisms associated with the toxicities of metal ions are very similar to the effects produced by many organic xenobiotics. Specific differences in the toxicities of metal ions may be related to differences in solubilities, absorbability, transport, chemical reactivity, and the complexes that are formed within the body. This review summarizes current studies that have been conducted with transition metal ions as well as lead, regarding the production of reactive oxygen species and oxidative tissue damage.

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    Debasis Bagchi received his M.Sc. degree in chemistry with a specialization in organic chemistry from Jadavpur University, Calcutta, India. He received his Ph.D. in medicinal chemistry from the Indian Institute of Chemical Biology (a national laboratory of the government of India), Calcutta. He conducted postdoctoral research at Bowling Green State University, Ohio and the University of Connecticut, Farmington from 1985 to 1988. He served as the Divisional Manager in research and development of Berger India Ltd., Calcutta, from 1982 to 1985 and again from 1988 to 1990. In 1991, he joined the Creighton University School of Pharmacy and Allied Health Professions faculty, and is currently an Assistant Professor in the Department of Pharmaceutical and Administrative Sciences. His research interests include mechanisms of toxicity of metals and various pesticides, and the design of novel chemoprotectants. Sidney J. Stohs received his B.S. in pharmacy and an M.S. degree in pharmacognosy from the University of Nebraska-Lincoln. He received his Ph.D. in biochemistry from the University of WisconsinMadison. He served on the faculty at the University of NebraskaLincoln from 1967 to 1975. He was a visiting professor at Krolinska Institute, Stockholm, Sweden in 1975 to 1976. From 1976 to 1989, he was at the University of Nebraska Medical Center, chairing the Department of Biomedicinal Chemistry from 1976 to 1985. He served as Assistant Dean for Research and Development in the Colege of Pharmacy from 1985 to1987. Dr. Stohs was a visiting scientist at the National Institute of Environmental Health Sciences in 1987 to 1988. He joined Creighton University Health Sciences Center as the Assistance Dean for Research in 1989, with appointments in the Department of Pharmaceutical Sciences and Pharmacology. He was appointed Dean of the School of Pharmacy and Allied Health Professions in 1990. His research interests include mechanisms of toxicity and the development of chemeprotective agents against toxins.

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