Pulmonary cadmium oxide toxicity in the rat.
Although occupational exposures to cadmium have usually involved inhalation of insoluble cadmium oxide (CdO) particles, experimental studies of pulmonary cadmium toxicity have relied on aerosol exposures to soluble cadmium chloride particles. The present study describes a model of acute lung injury based on single 3-h exposures of rats to 0.5 and 5.3 mg/m3 CdO. Biochemical changes were correlated with pathological observations for 15 d postexposure to CdO. Four days following CdO exposure, histopathological observations included focal areas of epithelial hyperplasia, a mononuclear interstitial infiltrate, and increased numbers of alveolar macrophages. In the high-dose group, these changes were correlated with increases in tissue protein and DNA contents of 217% and 195% of controls, respectively. While lungs from the low-dose exposures had returned to a normal appearance by 15 d postexposure, high-dose-exposed lungs exhibited an increase in noncellular thickening of the interstitium and a continued general hypercellularity at this time. In the high-dose exposure group, activities of the enzymes glutathione peroxidase, glutathione reductase, and the dehydrogenase of glucose 6-phosphate and 6-phosphogluconate were significantly elevated two- to fivefold at 2-4 d postexposure. When a correction was made for changes in lung cell number, significant increases were observed only in activities of the pentose-cycle dehydrogenases at 180-238% of controls. These increases suggested an enhanced ability of CdO-exposed lungs to generate the pentose-cycle products NADPH and ribose 5-phosphate, which would be needed for lipid and nucleic acid biosynthesis expected during the proliferative stages of epithelial repair. This study has demonstrated that the response to CdO exposure includes the induction of enzymatic activities that are related to antioxidant defense and lung repair.
D000395:Air Pollutants, Occupational / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D019187:Cadmium Compounds; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009249:NADP / Q000378:metabolism; D010087:Oxides; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000395:Air Pollutants, Occupational; D019187:Cadmium Compounds; D010087:Oxides; D002104:Cadmium; C029663:cadmium oxide; D009249:NADP; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase