Experimental production of diffuse pulmonary fibrosis and alveolitis in cattle: the effects of repeated dosage with 3, methyl indole.
Eleven Friesian steers were given 3, methyl indole (3MI) orally at dose rates ranging from 0.1 to 0.3 g/kg. Three of these (group B) received a single oral dose of 0.2 g/kg and subsequently developed respiratory distress. Their plasma 3MI concentrations six hours after dosing were between 2.25 and 7.23 micrograms/ml. The steer with the highest six-hour plasma value died at this stage and the dominant pathological feature was severe pulmonary oedema. The other two steers survived until they were slaughtered 96 hours after dosing; the major pathological findings in them were interstitial emphysema, hyaline membranes and alveolar epithelial hyperplasia. The other eight steers (group C) each received weekly oral doses of 0.1 g 3MI/kg for 10 weeks. One animal died after developing severe respiratory distress following its third dose. Thereafter, the others developed two separate patterns of response. Three steers (subgroup C1) became progressively more tolerant to oral 3MI, even in the face of dose rates increased to 0.2 and 0.3 g/kg during the 11th to 14th weeks of the study and also in the presence of relatively high plasma 3MI concentrations after dosing. One animal was slaughtered after its 10th dose and two after their 14th dose of 3MI; post mortem examinations revealed that their lungs were macro- and microscopically normal. The other steers (subgroup C2) all continued to react after each weekly oral dose of 3MI and their post-dosing plasma 3MI concentrations consistently remained relatively low. Latterly, each of the three steers which survived to the 14th week also exhibited persistent tachypnoea and marked hyperpnoea between dosings. On post mortem examination, in addition to the signs generally associated with acute 3MI toxicity (see above), each of the subgroup C2 steers were found to have diffuse pulmonary fibrosis and an alveolitis. While certain cattle appear to become tolerant to the effects of repeated doses of 3MI, the results of this study clearly demonstrated that, in others, such treatment eventually gives rise to diffuse pulmonary fibrosis and alveolitis.
D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000139:chemically induced* / Q000473:pathology; D004361:Drug Tolerance; D007211:Indoles / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D011016:Pneumonia, Atypical Interstitial, of Cattle / Q000139:chemically induced*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary*; D012119:Respiration / Q000187:drug effects; D012862:Skatole / Q000633:toxicity*
D007211:Indoles; D012862:Skatole