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

被引:61
作者
SCHAPIRA, RM
GHIO, AJ
EFFROS, RM
MORRISEY, J
ALMAGRO, UA
DAWSON, CA
HACKER, AD
机构
[1] CLEMENT J ZABLOCKI VET AFFAIRS MED CTR,PULM & CRIT CARE MED SECT,LAB SERV,MILWAUKEE,WI 53295
[2] MED COLL WISCONSIN,DIV PULM & CRIT CARE MED,MILWAUKEE,WI
[3] MED COLL WISCONSIN,DEPT PHYSIOL,MILWAUKEE,WI
[4] MED COLL WISCONSIN,DEPT PATHOL,MILWAUKEE,WI
[5] DUKE UNIV,MED CTR,DIV PULM & CRIT CARE MED,DURHAM,NC
关键词
D O I
10.1165/ajrcmb.12.2.7865220
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The hydroxyl radical (.OH) is a highly reactive oxygen free radical that has been implicated as a cause of lung injury following exposure to silica and silicates. Despite evidence that silica generates .OH in vitro, there has been no previous demonstration of in vivo production of .OH after exposure to nonfibrous mineral oxide dusts. We tested the hypothesis that instillation of silica into rat lungs is associated with greater .OH production and acute lung inflammation in vivo relative to the instillation of a less toxic non-silicate particle, titanium dioxide. The production of .OH in the lungs following dust instillation was measured using sodium salicylate as an . OH trap. Seven days after dust exposure, the rats were given intraperitoneal salicylate, the lungs isolated, and salicylate hydroxylation products (2,3- and 2,5-dihydroxybenzoic acid), reflecting .OH, were measured. There was significantly more 2,3-dihydroxybenzoic acid in silica-exposed lungs compared with lungs instilled with titanium dioxide. In addition, the instillation of silica into rat lungs in vivo was associated with a greater acute inflammatory response. We conclude that following in vivo exposure, silica stimulates greater .OH production relative to the less toxic particle, titanium dioxide. These differences in .OH generation correspond to disparities in acute lung inflammation.
引用
收藏
页码:220 / 226
页数:7
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