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The inhibition of silica-induced lung inflammation by dexamethasone as measured by bronchoalveolar lavage fluid parameters and peroxynitrite-dependent chemiluminescence.

Authors
Van Dyke-K; Antonini-JM; Wu-L; Ye-Z; Reasor-MJ
Source
Agents Actions 1994 Mar; 41(1/2):44-49
NIOSHTIC No.
00226675
Abstract
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.
Keywords
NIOSH-Publication; NIOSH-Cooperative-Agreement; Lung-disease; Lung-fibrosis; Lung-irritants; Chronic-inflammation; Silica-dusts; Laboratory-animals; Immune-system; Enzyme-activity
CODEN
AGACBH
CAS No.
14808-60-7
Publication Date
19940301
Document Type
Journal Article
Funding Amount
2937066
Funding Type
Cooperative Agreement
Fiscal Year
1994
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U60-CCU-306149
Issue of Publication
1/2
ISSN
0065-4299
Priority Area
Pulmonary-system-disorders
Source Name
Agents and Actions
State
DC
Performing Organization
Center to Protect Workers' Rights
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