Biochemical and histopathological changes in nasal epithelium of rats after 3-day intermittent exposure to formaldehyde and ozone alone or in combination.
To get a better insight into the pathophysiology of the nasal changes induced by formaldehyde-ozone mixtures, a 3-day inhalation study was carried out in rats, using intermittent exposure to formaldehyde (3.6 ppm) and ozone (0.4 ppm) alone or in combination and focusing on biochemical and histopathological changes in rat nasal respiratory epithelium. Formaldehyde dehydrogenase, glutathione S-transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities in this epithelium were not affected by the individual compounds. However, combined exposure to formaldehyde and ozone resulted in slightly decreased activities of these enzymes. Formaldehyde was found to induce rhinitis, degeneration, frank necrosis, hyperplasia and squamous metaplasia of the ciliated and non-ciliated nasal respiratory epithelium, while ozone induced disarrangement, flattening and slight basal cell hyperplasia of the non-ciliated cuboidal epithelium accompanied by influx of neutrophils. Proliferating cell nuclear antigen (PCNA) expression was elevated not only in nasal areas showing ozone-induced histopathological changes but also in the otherwise normal-appearing epithelium of the nasal septum. No interactive effects were found with respect to proliferative response of the nasal respiratory epithelium after exposure to the formaldehyde-ozone mixture. The present study did not provide evidence of a major role of glutathione and glutathione-dependent enzymes in the pathogenesis of nasal lesions induced by formaldehyde and/or ozone, demonstrated the potential of ozone to affect the mucociliary epithelium lining the nasal septum, and suggested that PCNA expression is a sensitive tool for detection of early effects of respiratory irritants.
Cassee
F R
FR
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, AJ Zeist, The Netherlands.
Feron
V J
VJ
D000280:Administration, Inhalation; D000444:Aldehyde Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D005557:Formaldehyde / Q000633:toxicity*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009296:Nasal Cavity / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis; D010126:Ozone / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D005557:Formaldehyde; D010126:Ozone; C020145:formaldehyde dehydrogenase (glutathione); D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; D005980:Glutathione Reductase; D005982:Glutathione Transferase