title: Characteristics of the acute-phase pulmonary response to silica in rats.
abstract: Exposure to silica, a cytotoxic and fibrogenic mineral dust, has been demonstrated to cause pulmonary inflammation and damage to the lung tissue. In contrast to the long-term consequences, little information exists on the sequence of inflammatory/damaging events occurring acutely after exposure to silica. The purpose of this study was to determine the minimum time after the administration of silica that the inflammatory/damage response is detectable and the temporal relationship of these processes. Male Fischer 344 rats were dosed intratracheally with silica (2.5 or 10 mg/100 g body weight) or saline vehicle. At 2 and 4 h after instillation, both cellular (total cell count and neutrophil count) and biochemical (total protein, albumin, and beta-glucuronidase and lactate dehydrogenase activities) parameters of inflammation and damage were evaluated in the bronchoalveolar lavage fluid. At 2 h, total protein levels were elevated at both silica doses, but all other parameters were unchanged; however, 4 h after silica exposure all parameters were elevated over those of the saline control. In a further attempt to characterize the inflammatory/damage processes, luminol-dependent chemiluminescence (LDCL) was performed on aliquots of chopped lung. At 2 h after silica instillation, phorbol myristate acetate-stimulated lung tissue from silica-treated rats had no increase in light production when compared to controls, whereas after 4 h there were significant increases in LDCL activity in both dose groups when compared to controls. The addition of superoxide dismutase (SOD) decreased LDCL activity of the 2.5 mg/100 g group by 59% (2 h) and 66% (4 h), and of the 10 mg/100 g group by 49% (2 h) and 73% (4 h). Alternatively, the addition of N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, decreased the 2.5 mg/100 g group by 52% (2 h) and 60% (4 h). The 10 mg/100 g group was decreased by 67% (2 h), but only exhibited a 12% reduction at 4 h. SOD and L-NAME also inhibited the background LDCL in saline-treated rats. These reductions in LDCL activity indicate that reactive oxygen and nitrogen species play a role in the acute phase pulmonary response from silica. The results of this study indicate that the initial stages of damage begin to appear by 2 h, but damage and inflammation are definitive by 4 h after administration of silica in rats.
authors.affiliation: Robert C. Byrd Health Sciences Center, West Virginia University, Department of Pharmacology and Toxicology, Morgantown 26506-9223, USA.
authors.forename: M
authors.initials: M
authors.lastname: DiMatteo
authors.forename: J M
authors.initials: JM
authors.lastname: Antonini
authors.forename: K
authors.initials: K
authors.lastname: Van Dyke
authors.forename: M J
authors.initials: MJ
authors.lastname: Reasor
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D005966:Glucuronidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008163:Luminescent Measurements; D008165:Luminol / Q000737:chemistry; D008168:Lung / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
chemical_list: D000418:Albumins; D011506:Proteins; D008165:Luminol; D012822:Silicon Dioxide; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005966:Glucuronidase; D013755:Tetradecanoylphorbol Acetate; D019331:NG-Nitroarginine Methyl Ester