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Pathology and glutathione status in 3-methylindole-treated rodents
J D Adams1, W W Laegreid, J C Huijzer
1Pharmacology/Toxicology Program, Washington State University, Pullman 99164.
Abstract:
Light and electron microscopic studies were performed to assess the pathology induced by 3-methylindole (3MI) in Sprague-Dawley rats and Swiss-Webster mice. Rats have not been established as a susceptible species to 3MI-induced pulmonary damage, whereas mice are known to be a good model for this pneumotoxicity. Therefore, mice were used as a comparison species for pneumotoxicity studies in the rat. Rats were as susceptible to 3MI-mediated toxicity as mice. The loss of Clara cells in the bronchiolar epithelium was the major pulmonary lesion in both species. Alveolar cells in the lungs of either species were not damaged. The only other lesion in the rat was that the nasal epithelium was totally eroded in caudal areas of the sinuses. Glutathione was depleted by 3MI in pulmonary tissues of mice and rats. Maximal depletion (53% of control values) occurred in rat lung. This work demonstrates that both rodent species are susceptible to 3MI-induced pulmonary damage.
Insights
This study shows that both rats and mice are susceptible to lung damage from 3-methylindole (3MI). The primary injury observed was the loss of Clara cells in the airways of both species.
Area of Science:
- Toxicology
- Pulmonary Pathology
- Comparative Medicine
Background:
- 3-methylindole (3MI) is a known pulmonary toxicant, with mice serving as a standard model for 3MI-induced pneumotoxicity.
- Rats have not been extensively studied for susceptibility to 3MI-induced lung injury.
Purpose of the Study:
- To investigate and compare the susceptibility of Sprague-Dawley rats and Swiss-Webster mice to 3-methylindole (3MI)-induced pulmonary and nasal pathology.
- To evaluate the role of Clara cells and glutathione depletion in 3MI toxicity in these rodent models.
Main Methods:
- Light and electron microscopy were employed to examine lung and nasal tissues from rats and mice exposed to 3MI.
- Glutathione levels in pulmonary tissues were measured to assess biochemical changes.
Main Results:
- Contrary to expectations, rats exhibited susceptibility to 3MI toxicity, comparable to mice.
- The principal pulmonary lesion in both species was the loss of Clara cells in the bronchiolar epithelium, with no damage to alveolar cells.
- Significant depletion of glutathione was observed in the lungs of both rats and mice following 3MI exposure, with maximal depletion in rats.
Conclusions:
- Both rats and mice are susceptible to 3-methylindole-induced pulmonary damage.
- Clara cell loss is a key feature of 3MI pneumotoxicity in these species.
- 3MI also induces nasal epithelial erosion in rats and glutathione depletion in the lungs of both species.