Comparison of inducible nitric oxide synthase gene expression and lung inflammation following intratracheal instillation of silica, coal, carbonyl iron, or titanium dioxide in rats

Journal of Toxicology and Environmental Health
J A BlackfordV Castranova

Abstract

The pulmonary toxicity of the respirable dusts silica, coal, carbonyl iron, and titanium dioxide on alveolar macrophage (AM) and neutrophil (PMN) inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production was investigated. Rats were intratracheally instilled with 5 mg/100 g body weight of silica, coal, carbonyl iron, or titanium dioxide. The dust particles averaged less than 5 microns in diameter. Bronchoalveolar lavage was performed 24 h later. Bronchoalveolar lavage cell (BALC) differentials, iNOS gene expression and NO production by BALC (measured indirectly as NO-dependent chemiluminescence), and lavageable lung protein levels were measured. Analyzed on an equal mass basis, silica, coal, and titanium dioxide dusts increased the production of iNOS-dependent NO by AM. Silica and titanium dioxide both increased the levels of iNOS mRNA while carbonyl iron and coal did not. Each dust caused an increase in PMN, indicating an inflammatory response. Carbonyl iron and titanium dioxide decreased the numbers of AM. Levels of acellular lavageable lung protein were increased by silica, carbonyl iron, and titanium dioxide. When exposure was normalized for an equal number of particles, the pneumotoxic dusts, s...Continue Reading

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