Abstract

Young, male rats were administered monocrotaline (MCT) ad libitum in the drinking water (22 μg/ml) for up to 28 days, and the development of toxicity in lung, liver, and kidney was examined. Clearance of perfused 5-hydroxytrytptamine by isolated lungs of treated rats was decreased as early as 14 days. This was accompanied by increases in lung/body weight ratio and in lactate dehydrogenase activity in cell-free bronchopulmonary lavage fluid. Hypertrophy of the right heart and increased inflow perfusion pressure of isolated lungs were apparent by 21 days of MCT treatment. The magnitude of the changes in all of these parameters increased with duration of treatment. After 28 days of treatment biliary indocyanine green excretion was decreased and plasma glutamic pyruvic transaminase activity was slightly elevated. Twenty-eight days of treatment also resulted in elevated blood urea nitrogen, decreased accumulation of p-aminohippuric acid by kidney slices, and increased accumulation of tetraethylammonium by kidney slices. Thus, lung, liver, and kidney are each affected by this MCT treatment regimen, and functional effects on lung precede effects on other tissues.

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