HYDROXYL RADICAL PRODUCTION AND LUNG INJURY IN THE RAT FOLLOWING SILICA OR TITANIUM-DIOXIDE INSTILLATION IN-VIVO

The hydroxyl radical (.OH) is a highly reactive oxygen free radical th at has been implicated as a cause of lung injury following exposure to silica and silicates. Despite evidence that silica generates .OH in v itro, there has been no previous demonstration of in vivo production o f .OH after exposure to nonfibrous mineral oxide dusts. We tested the hypothesis that instillation of silica into rat lungs is associated wi th greater .OH production and acute lung inflammation in vivo relative to the instillation of a less toxic non-silicate particle, titanium d ioxide. The production of .OH in the lungs following dust instillation was measured using sodium salicylate as an . OH trap. Seven days afte r dust exposure, the rats were given intraperitoneal salicylate, the l ungs isolated, and salicylate hydroxylation products (2,3- and 2,5-dih ydroxybenzoic acid), reflecting .OH, were measured. There was signific antly more 2,3-dihydroxybenzoic acid in silica-exposed lungs compared with lungs instilled with titanium dioxide. In addition, the instillat ion of silica into rat lungs in vivo was associated with a greater acu te inflammatory response. We conclude that following in vivo exposure, silica stimulates greater .OH production relative to the less toxic p article, titanium dioxide. These differences in .OH generation corresp ond to disparities in acute lung inflammation.