Characteristics of the acute-phase pulmonary response to silica in rats.
DiMatteo-M; Antonini-JM; Dyke-K; Reasor-MJ
J Toxicol Environ Health, A 1996 Jan; 47(1):93-108
Early pulmonary response to intratracheal instillation of silica (14808607) particles was characterized by bronchoalveolar lavage fluid (BALF) analysis and luminol dependent chemiluminescence (LDCL). Male Fischer-344-rats were intratracheally instilled with 0, 25 or 100mg/kg silica. BALF total protein was significantly increased two fold 2 hours (hr) after treatment at both doses and 2.5 fold after 4hr at the higher exposure. The 4hr total protein level was significantly elevated relative to the 2h level at the 100mg/kg dose. A significant 2.5 fold increase in BALF albumin was observed 4hr after the 100mg/kg dose. BALF gamma-glucuronidase activity was significantly increased two and four fold by 25 and 100mg/kg doses, respectively, 4hr after instillation. BALF lactate- dehydrogenase activity was significantly increased two and six fold by 25 and 100mg/kg silica, respectively, after 4hr. Total BALF cell numbers were significantly increased after 4hr in the 100mg/kg group, with a seven fold increase in neutrophils. The 4hr neutrophil increase represented a significant 4.5 fold increase over the 2hr levels. Significant four and seven fold increases at the 25 and 100mg/kg doses, respectively, were measured in phorbol-myristate- acetate (PMA) stimulated LDCL activity 4hr after instillation. The LDCL activity of unstimulated lung tissue from 100mg/kg treated rats, 4hr after instillation, was significantly six fold greater than 2h posttreatment and four fold greater than controls. Inhibition of PMA stimulated LDCL by superoxide-dismutase was 58.9% and 66.2% for the 25mg/kg, 2 and 4hr posttreatment groups, respectively, and 49.3% and 73.1% for the 100mg/kg 2 and 4hr posttreatment groups, respectively. Inhibition of PMA stimulated LDCL by N-omega-nitro-L-arginine-methyl-ester was 52.3% and 60.2% for the 25mg/kg, 2 and 4hr posttreatment groups, respectively, and 66.6% and 12.1% for the 100mg/kg 2 and 4hr posttreatment groups, respectively. The authors conclude that pulmonary damage is evident within 2hr and inflammation occurs within 4hr of silica exposure.
NIOSH-Publication; NIOSH-Cooperative-Agreement; Silica-dusts; Pulmonary-disorders; In-vivo-study; Laboratory-animals; Acute-exposure; Physiological-response; Lung-cells; Alveolar-cells
Michael DiMatteo, Robert C. Byrd Health Sciences Center of West Virginia University, Department of Pharmacology and Toxicology, P.O. Box 9223, Morgantown, WV 26506-9223, USA
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