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The inhibition of silica-induced lung inflammation by dexamethasone as measured by bronchoalveolar lavage fluid parameters and peroxynitrite-dependent chemiluminescence.
Van Dyke-K; Antonini-JM; Wu-L; Ye-Z; Reasor-MJ
Agents Actions 1994 Mar; 41(1/2):44-49
An animal model for studying the ability of anti inflammatory steroids to reduce the pneumotoxicity induced by silica (14808607) was described. The potent anti inflammatory steroid dexamethasone (DEX) was administered to male Fischer-344-rats before intratracheal instillation of silica to inhibit the induction of nitric-oxide- synthase (NOS) and thus block the production of the potent oxidant, peroxynitrite. The dose of DEX was 20mg/kg given on days one, three, and five. On day six, the animals were intratracheally instilled with silica (20 milligrams/0.5 milliliters saline vehicle) or saline alone. Lung damage was assessed by luminol dependent chemiluminescence (LDCL) of the cells and by measuring total number of cells, total protein, neutrophils, and lymphocytes. Twenty four hours after silica treatment, a profound inflammatory response resulted in the nonsteroid group, characterized by increases in total protein, total number of cells, neutrophils, lymphocytes and LDCL. Pretreatment with DEX completely inhibited the silica induced elevation of LDCL. Superoxide-dismutase (SOD), which catalyzes the breakdown of superoxide anion, and N-nitro-L-arginine-methyl-ester- hydrochloride (NAME), an inhibitor of NOS, both inhibited the LDCL response. The inhibition of LDCL by NAME suggested that a portion of this silica induced oxidative response resulted from NO. Superoxide and NO combine to produce peroxynitrite, which is involved in the LDCL response. The researchers conclude that pretreatment of rats with the steroid DEX prevents the acute inflammatory reaction of silica. The results indicated that the steroid's effect may in part be mediated by inhibition of the induction of NOS. Currently, no effective treatment exists for workers who have been exposed to silica inhalation.
NIOSH-Publication; NIOSH-Cooperative-Agreement; Lung-disease; Lung-fibrosis; Lung-irritants; Chronic-inflammation; Silica-dusts; Laboratory-animals; Immune-system; Enzyme-activity
Issue of Publication
Agents and Actions
Center to Protect Workers' Rights
Page last reviewed: April 12, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division