Pulmonary changes in rats following administration of 3-methylindole in cremophore EL

Abstract

3-methylindole (3-MI) dissolvcd in the lipopliilic carrier Crcmophorc EL was administered intraperitoneally to male, twelve-week-old Sprague- Dawley rats. Gross and histopathologic changes in the lurigs were studied using light microscopy rit thrcc timepcriods fc>llowing administration: 16, 24. and 46 hours. Both 3-MI1 and Cremophore caused changes in bronchiolar epithelium at 16 hours. By 46 hours, Cremophore-injected rats showed no effects of the carrier; whercas, 3-MI rats showed severe lung changes characterizcd by aii-way epithelial and pulmonary vascular endothelial nccrosis and slougliing, cellular infiltration by lyniphocytes and macrophages. perivascular edema, alveolar edema, and lymph stasis. Grossly, the controls showed no effect of the carrier and nonc died during the st~idiesI. n contrast, 3-MI injected rats quickly became lethargic and displayed tachypiiea. anorexia, and progressivc respiratory distress. Two of five 3-M1 rats in the final group died just prior to 46 hours. Al1 of this group had grossly congested lungs and ninrked pleural effusion. The lesions and timc course showed similarities to those observed in ruminants and mice. We conclude thnt 3-M1 in Cremophore causes an acute 1"-ogressive pneumonitis in rats and suggest that the rats niay be a suitable model for 3-MI-induced and similar tosic lung diseases in domestic animals and people