Acute inflammation and recovery in rats after intratracheal instillation of a 1-->3-B-glucan (zymosan a).
Robinson-VA; Young-S; Barger-M; Porter-DW; Goldsmith-R; Frazer-DG; Castranova-V
Toxicologist 2001 Mar; 60(1):197
1-->3 B-Glucans derived from the inner cell wall of yeasts and fungi have been implicated in organic dust toxic syndrome. However, animal studies report conflicting results concerning the inflammatory potency of 1-->3-B-glucan. In this experiment, we assessed the pulmonary reaction of rats to 1-->3-B-glucan (zymosan A) exposure. Male Sprague-Dawley rats were exposed via intratracheal instillation (IT) to zymosan A (dose range: 0-5 mg/kg body weight). Rats were sacrificed 1-7 days post-exposure and the following pulmonary responses monitored: (1) breathing frequency (2) differential cell counts of bronchoalveolar lavage (BAL) cells, (3) chemiluminescence (CL) as a measure of alveolar macrophage activation, (4) nitric oxide production by alveolar macrophages, and (5) albumin and (6) lactate dehydrogenase (LDH) levels in the first lavage fluid. Upon challenge with zymosan A, rats exhibited a dose-dependent pulmonary response at one day post IT which was significantly higher than the control level at a dose of 1 mg/kg body weight. Post-IT breathing frequencies and polymorphonuclear leukocytes (PMN) obtained by BAL both correlated very well with zymosan A concentration (r2=0.95 and 0.99 respectively). Albumin and LDH levels of the acellular BAL fluid correlated (r2 = 0.80) with the dose of zymosan. The recovery from a single intratracheal administration of zymosan A (2.5 mg/kg body weight) was monitored over 7 days. PMN and CL showed significant recovery from the day 1 level by 3 days post-exposure. Breathing frequencies and nitric oxide production showed significant recovery from the day 1 level by 4 days post-exposure. A good correlation (r2 = 0.8) between PMN in BAL, CL, or nitric oxide production and the days post-exposure was observed.
Acute-exposure; Animal-studies; Laboratory-animals; Laboratory-testing; Organic-dusts; Pulmonary-system; Exposure-levels
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California