Clofibrate increases the number of peroxisomes and of lamellar bodies in alveolar cells type II of the rat lung.
The hypolipidemic drug clofibrate, which causes a striking proliferation of hepatic peroxisomes, and the induction of peroxisomal lipid metabolizing enzymes, was tested for its influence on rat lung. Alveolar cells type II of the lung are the major source of the surface-active phospholipid-apoprotein complex. Their surfactant-containing lamellar bodies are part of the pulmonary surfactant system. To test the possible relationship between lung peroxisomes and the phospholipid-rich lamellar bodies in alveolar cells type II, clofibrate was administered to male rats. Drug treatment for 7 days resulted in a 30% (p less than 0.001) increase in the number of lamellar bodies within the type II cells, as estimated by morphometry on semithin sections of the lung. In contrast, the average number of type II cells per area of lung remained unchanged which indicates that type II cell proliferation did not occur. Intraalveolar macrophages were consistently vacuolated and markedly increased in size in the lungs of the treated rats. Peroxisomes (microperoxisomes) were identified cytochemically using the alkaline diaminobenzidine (DAB) method for catalase, a marker enzyme of these organelles. Ultrastructural-morphometric analysis of the lungs showed that clofibrate treatment resulted in a 60% increase in the profile number of DAB-positive peroxisomes (p less than 0.005) in alveolar cells type II which are known to be actively involved in the synthesis of the pulmonary surfactant. The number of mitochondria remained unchanged. A great variation in shape and size of the proliferated peroxisomes was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Fringes
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Institute of Pathology, University of Freiburg/Federal Republic of Germany.
Gorgas
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K
Reith
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A
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology*; D006651:Histocytochemistry; D008168:Lung / Q000201:enzymology; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D008854:Microscopy, Electron; D009940:Organoids / Q000187:drug effects / Q000648:ultrastructure*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D051381:Rats; D011917:Rats, Inbred Lew
D002374:Catalase; D002994:Clofibrate