Free Radical Generation By Metal Ions Adsorbed On Mineral Dust: A Mechanism For Chronic Lung Injury1

Metal ions, such as chromium (Cr) and vanadium (V) are found as trace impurities in mineral dust. Since metal ion mediated free radical generation has been implicated in many disease processes, we carried out a detailed investigation of the metabolism of these metal ions by biological redox systems and the possible oxygenated radical generation therefrom. We found that highly reactive Cr(5+) species are generated in the reduction of Cr(6+) by NADPH-dependent glutathione reductase, lipoyl dehydrogenase, and ferredoxin-NADP+ oxidoreductase. The reduced metal ion species react with hydrogen peroxide, to generate hydroxyl (•OH) radicals in a continuous cycle. The enzymatic catalysis processes also involves the reduction of molecular oxygen to the superoxide [(0-1 2)] radical. Thus only a trace amount of metal ions chemisorbed on mineral dusts, such as quartz, can catalyze the generation of the highly toxic oxygenated radical species from cellular hydrogen peroxide, suggesting a new biochemical mechanism for mineral dust induced chronic lung injury.