Role of Reactive Oxygen Radicals in Silica Cytotoxicity

"Inhalation of crystalline silica is associated with a biphasic biologic response of acute cell injury and chronic pulmonary fibrosis. Dust induced cell membrane injury leading to the release of lysosomal enzymes and cell death has been implicated as the initial important biologic event triggering the fibrosis. However, it ls also possible other biologic reactions could alternatively, or in addition to these enzyme related cytotoxicity reactions, alter the normal functioning of cells. It is well known that phagocytic activation results in the production of oxygen radicals which are highly cytotoxic to cells. In healthy - lung, protection against the toxic effects of the normal balanced ·biologic reactions are provided by a number of defen1e systems including antioxidants. In disease or condition of overproduction of oxygen radicals, biochemical protection may be overwhelmed with resultant cellular injury.Our recent observations have shown that reactive oxygen radicals (ROR) are generated during grinding of crystalline silica. We hypothesized that these newly generated RORs may cause cell injury, lipid peroxidation, or even damage to macromolecules such as DHA. Biochemical aberrations caused by the inhalation of crystalline silica with ROR at occupational settings might overwhelm cellular and antioxidant defense systems of the lung leading to injury and subsequent fibrosis.To test this hypothesis, we have investigated the generation and decay of ROR produced by crystalline silica using electron spin resonance (ESR) and investigated its toxicity with conventional biologic tests at various time intervals after grinding. We also studied the decay of these newly generated RORs in buffer and the effect of antioxidants and scavengers in the abolition of cellular damages."