Generation of oxygen radicals and mechanisms of injury prevention.
Exposure to crystalline silica can result in damage to the lung parenchyma and scarring that can lead to fibrosis. Pulmonary damage may be the direct consequence of toxic interaction between quartz particles and cell membranes, or it may be due to silica-induced production of oxidant species by pulmonary phagocytes, that in turn overwhelms pulmonary antioxidant systems and causes lung injury. Data indicate that grinding or fracturing quartz particles breaks Si-O bonds and generates .Si and Si-O. radicals on the surface of the cleavage planes. Upon contact with water, these silica-based radicals can generate hydroxyl radicals (.OH). These surface radicals decay as fractured silica dust is aged. Freshly fractured quartz is significantly more potent than aged silica in directly causing lipid peroxidation, membrane damage, and cell death. Furthermore, freshly ground silica is a more potent stimulant of alveolar macrophages than aged silica. This silica-induced activation results in the production of superoxide (O2-), hydrogen peroxide (H2O2), nitric oxide (NO.), and other oxidant species that can damage lung cells. Tetrandrine, an herbal medicine that exhibits antifibrotic activity in rat models of silicosis, effectively blocks the ability of quartz to stimulate oxidant release from pulmonary phagocytes.
Castranova
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Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505.
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D044182:Benzylisoquinolines; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D008171:Lung Diseases / Q000209:etiology* / Q000517:prevention & control*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012822:Silicon Dioxide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity
D000470:Alkaloids; D044182:Benzylisoquinolines; D003497:Cyclic N-Oxides; D005609:Free Radicals; D017382:Reactive Oxygen Species; C009438:tetrandrine; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D012822:Silicon Dioxide