Attenuation of acute inflammatory effects of silica in rat lung by 21-aminosteroid, U74389G.

Abstract:

:Chemical alteration of the glucocorticoid, methylprednisolone, has led to the introduction of a new class of compounds called the 21-aminosteroids (21-ASs). The purpose of this study was to investigate the effect of the 21-AS, U74389G, on silica-induced acute lung injury. Male Fischer 344 rats were treated intraperitoneally with saline or U74389G in a total dose of 15 mg/kg divided into three injections of 5 mg/kg separated by 4 h. Following the first treatment, animals from the two groups were intratracheally instilled with silica (10 mg/100 g body wt in 0.5 ml of saline) or saline vehicle (0.5 ml). Twenty-four hours after the instillations, bronchoalveolar lavage (BAL) was performed. In the animals not receiving U74389G, marked increases in total protein, beta-glucuronidase, and lactate dehydrogenase (LDH) activities and number of neutrophils (PMNs) were demonstrated in the BAL fluid of the silica-treated animals compared to their controls. Silica also caused dramatic increases in the luminol-dependent chemiluminescence (CL) of lung tissue and BAL cells. The CL reaction was decreased by superoxide dismutase (SOD) and N-nitro-L-arginine methyl ester hydrochloride (L-NAME), a nitric oxide (NO) synthase inhibitor. In animals treated with U74389G, there was attenuation of the silica-induced increases in biochemical, cellular, and chemiluminescent indices of damage. This study demonstrates that U74389G significantly reduces acute lung injury caused by the intratracheal instillation of silica, and this drug may be of potential value for treatment of lung diseases in which damage caused by reactive oxygen species has been implicated.

journal_name

Inflammation

journal_title

Inflammation

authors

Antonini JM,van Dyke K,DiMatteo M,Reasor MJ

doi

10.1007/BF01534376

subject

Has Abstract

pub_date

1995-02-01 00:00:00

pages

9-21

issue

1

eissn

0360-3997

issn

1573-2576

journal_volume

19

pub_type

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