Experimentally induced bleomycin sulfate pulmonary toxicity: histopathologic and ultrastructural study in the pheasant

Abstract

Morphological alterations in the lungs of pheasants after prolonged high-dosage administration of bleomycin sulfate were studied by light and electron microscopy. Nontreated birds acted as controls, and their lungs showed no abnormalities. Lungs of bleomycin-treated pheasants revealed collapse alternating with overexpansion, marked cuboidalization of atrial epithelium, and incipient interstitial fibrosis. There were neither lymphoplasmacytic or eosinophilic infiltrates, nor evidence of vasculitis. Ultrastructurally, type 1 alveolar epithelial cells were either reactive or conspicuously absent in the air capillaries. Type 2 alveolar epithelial cells appeared hyperplastic with numerous lamellar bodies, many of which extruded into air spaces. Immature fibroblasts were noted in the vicinity of collagen fibrils or amorphous material resembling elastin. No immune deposits were present in basement membranes. These findings are consistent with a direct toxic effect of bleomycin to the pheasant lung rather than a drug hypersensitivity reaction. Reproduction of the bleomycin lesion in a nonmammalian species corroborates even further the high propensity of the drug to affect the lung.