Detection of Hydroxyl Radical Formation in Aqueous Suspensions of Fresh Silica Dust and Its Implication to Lipid Peroxidation in Silicosis

"Cellular damage induced by silica dust is known to be associated with increased fragility and destabilization or destruction of the cell membranes. The mechanism by which silica dust effects biological membranes is still unknown. Using the ESR spin-trap methodology, we find that hydroxyl radicals are generated in aqueous suspensions of freshly ground silica. The amount of the radicals generated depends on the extent of grinding and ""freshness"" of the dust. Using linoleic acid as a model lipid, we show that the silica dust causes lipid peroxidation via ·OH, 02-, or linoleic acid related radicals as intermediates. Catalase and superoxide dismutase inhibit the formation of these radicals. The results suggest that free radicals associated with freshly ground silica and the related lipid peroxidation of the memberanes may be the starting point of the silicotic processes.INTRODUCTIONDespite considerable-effort over the years, the mechanism by which the quartz particles exert their toxic action on cells and the process(es) by which these actions progress to fibrosis are still not fully understood (1,2). It is generally thought, nevertheless, that the interaction of the quartz particles with the cell membranes is the starting point of the silicotic process (3). We felt that the mechanism of the membrane damage by quartz might involve oxygenated free radicals because (a) a suspension of quartz particles in contact with alveolar macrophages has been reported.(4,5) to initiate an enhancement of lipid peroxidation, defined broadly as the ;oxidative deterioration of polyunsaturated components of lipids, and (b) hydroxyl (·OH) radicals are known to be capable of peroxidation by abstracting hydrogen atoms from cell-membrane lipids (6) and initiating lipid peroxidation in lysosomal membranes (7). Moreover it is known that exposure of cell membranes, fatty acids and unsaturated food oils to ionizing radiation, which generates ·OH. radicals, causes rapid peroxidation (6). Earlier studies o~ the aqueous chemistry of quartz suspensions have reported detection of HzOz (8), implicating the formation of ·OH radicals as transient species, but, we are not aware of any report of the detection of ·OH radicals in quartz suspensions and this provided the motivation for the present undertaking. Since it is known that, because of their high reactivity (hence short life time) in aqueous media, the ·OH radicals cannot be detected via electron spin resonance (ESR) directly (9,10), we have used ESR combined with the spin-trap methodology (9) for studying the •OH formation."