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Pulmonary changes in rats following administration of 3-methylindole in cremophore EL
A L Kiorpes1, I M Keith, R R Dubielzig
1Dept. Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706.
Abstract:
3-methylindole (3-MI) dissolved in the lipophilic carrier Cremophore EL was administered intraperitoneally to male, twelve-week-old Sprague-Dawley rats. Gross and histopathologic changes in the lungs were studied using light microscopy at three time-periods following administration: 16, 24, and 46 hours. Both 3-MI and Cremophore caused changes in bronchiolar epithelium at 16 hours. By 46 hours, Cremophore-injected rats showed no effects of the carrier; whereas, 3-MI rats showed severe lung changes characterized by airway epithelial and pulmonary vascular endothelial necrosis and sloughing, cellular infiltration by lymphocytes and macrophages, perivascular edema, alveolar edema, and lymph stasis. Grossly, the controls showed no effect of the carrier and none died during the studies. In contrast, 3-MI injected rats quickly became lethargic and displayed tachypnea, anorexia, and progressive respiratory distress. Two of five 3-MI rats in the final group died just prior to 46 hours. All of this group had grossly congested lungs and marked pleural effusion. The lesions and time course showed similarities to those observed in ruminants and mice. We conclude that 3-MI in Cremophore causes an acute progressive pneumonitis in rats and suggest that the rats may be a suitable model for 3-MI-induced and similar toxic lung diseases in domestic animals and people.
Insights
3-methylindole (3-MI) causes severe lung damage in rats, including airway and vascular damage, leading to pneumonitis. This study suggests rats are a suitable model for studying toxic lung diseases.
Area of Science:
- Toxicology
- Pulmonary Pathology
- Animal Models
Background:
- 3-methylindole (3-MI) is a compound known to cause lung toxicity in various species.
- Understanding the toxicological effects of 3-MI is crucial for both veterinary and human medicine.
Purpose of the Study:
- To investigate the pulmonary effects of 3-methylindole (3-MI) administered with Cremophore EL in Sprague-Dawley rats.
- To evaluate the suitability of rats as an animal model for 3-MI-induced lung disease.
Main Methods:
- Male Sprague-Dawley rats were administered 3-MI dissolved in Cremophore EL intraperitoneally.
- Lung tissues were examined using light microscopy at 16, 24, and 46 hours post-administration.
- Gross and histopathological changes were documented and compared to control groups.
Main Results:
- Both 3-MI and Cremophore EL induced initial bronchiolar epithelial changes at 16 hours.
- By 46 hours, 3-MI caused severe lung pathology, including epithelial and endothelial necrosis, inflammation, edema, and lymph stasis.
- 3-MI treated rats exhibited clinical signs of respiratory distress, with some mortality, while controls showed no adverse effects.
Conclusions:
- 3-methylindole in Cremophore EL induces acute, progressive pneumonitis in rats.
- The observed lung lesions and time course resemble those seen in ruminants and mice, supporting rats as a relevant model for 3-MI-induced lung diseases.