Pathogenesis and modification of cadmium-induced lung injury in mice

The effects of hyperoxia on Cd-damaged mouse lungs were studied to determine if there was potentiation of the injury by O₂. Female Balb/c mice were exposed to aerosols of 0.65% CdCl₂ for one hour by the nose-only method while control animals were exposed to water aerosols. Immediately after, some animals were placed in 70 to 80% O₂ for 5 days, while others were left in room air. Lung injury was determined by two biochemical methods, the hydroxyproline assay and ¹⁴ '^C-thymidine uptake by DNA, as well as by histopathological examinations and lung function studied. Cell kinetic studies of parenchymal and bronchiolar labelling index (LI) and cell differentiation following autoradiography were also done. The O₂ caused a delay in cell proliferation, but following removal from the O₂, cell proliferation increased and remained higher than controls for 15 days. Cd exposed animals had significantly increased levels of hydroxyproline/lung, indicative of increased collagen secretion and hence fibrosis. The Cd + O₂ exposed animals had even higher levels showing the synergistic effects of O₂. The histopathological studies at 3 weeks for Cd + air animals showed multifocal areas of interstitial and peribronchiolar fibrosis. For Cd + O₂ animals, the lesions were similar except for greater consolidation. The parenchymal LI in the Cd + O₂ group peaked at a later time than the Cd + O₂ group. The cell differentiation studies with Cd showed a delay in the peak of Type II epithelial and endothelial cell division when followed by the O₂ treatment. Experiments on the effects of prednisolone and X radiation in modifying the Cd-induced injury were also done but neither showed any alteration of the Cd-induced lesion. Pretreatment with 1 mg/kg of Cd i.p. for 4 days before Cd inhalation was also shown not to alter fibrosis. Investigations were made of the long term effects of Cd + O₂ group on the fibrotic lesion. Mechanisms of the action of Cd, and a literature survey are included. The study provides an experimental model for the interactions of two inhalants, Cd and O₂, and elucidates the behavior of different cell populations following injury.