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Partial protection from acute silica toxicity by dexamethasone in rats.

DiMatteo-M; Reasor-MJ
Toxicologist 1995 Mar; 15(1):97
The generation of silica dust and human exposure to this dust is of great occupational concern because it causes pulmonary inflammation/damage that ultimately proceeds to fibrosis. The initial phase of the toxic response occurs within 2 hours of exposure although the "classical" sign of inflammation (neutrophil influx) is absent. The purpose of this study was to differentiate between the toxicities due to the intrinsic properties of silica, and those due the cellular-infiltration. Male Fischer 344 rats were intratracheally (i.t.) instilled with silica (10 mg/100 g bw) or saline vehicle. Two hours post-instillation, half of each group received either steroid (dexamethasone 8 mg/kg, i.p.), in an attempt to suppress cellular infiltration and function, or saline vehicle. Post treatment continued on alternate days. Animals were killed on day 2 or 8 prior to that day's scheduled injection. Cellular (total and differential cell counts) biochemical (b-glucuronidase [b-glu] and albumin) parameters of inflammation/damage were evaluated in the broncho-alveolar lavage (BAL). At 2 days, silica caused a neutrophilia that was reversed by continued steroid injections up to day 8. BAL albumin and b-glu were significantly elevated in response to silica at both times despite the presence of steroid. These data suggest the intrinsic properties of silica play a primary role in the toxicities following i.t. instillation. However, the transient cellular influx at day 2 may initiate the inflammatory cascade. To eliminate the early influx of cells, a steroid pre-treatment was employed in addition to the post-treatment. Rats received i.p. steroid or saline on days -5, -3, and -1. On day 0, rats from each group received i.t. silica or saline. Two hours after the instillations and on alternate days after, rats received i.p. steroid or saline identical to pre-treatment. On days 2 and 8 the cellular response to silica was suppressed by steroid, but b-glu activity was significantly elevated. Although elevated over control levels, BAL albumin content of the steroid/silica group, at days 2 and 8, was markedly suppressed when compared to values from the steroid post-treatment protocol. The addition of the steroid pre-treatment seems to afford a greater protective effect than does the post-treatment alone, implicating the cells as well as the silica itself contribute to the toxic response.
Laboratory-animals; Animal-studies; Quartz-dust; Silica-dusts; Dust-particles; Dust-exposure; Particulate-dust; Airborne-particles; Fibrosis; Pulmonary-system-disorders; Respiratory-system-disorders; Respirable-dust
Publication Date
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Funding Type
Cooperative Agreement
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Issue of Publication
Source Name
The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland
Performing Organization
Center to Protect Workers' Rights