Biochemical and histological alterations in rats after acute nitrogen dioxide intoxication.
1. In previous studies a rat inhalation model was developed to investigate the treatment of acute nitrogen dioxide (NO2) intoxication. 2. Biochemical parameters, which may be important for the evaluation of lung injury and repair, were reviewed and compared with the histology. 3. After exposure to high NO2 concentrations (75 ppm, 125 ppm or 175 for 10 min) the lung injury observed by light microscope was most pronounced after 24 h and became worse with increasing concentration. 4. The most sensitive indicators for lung injury in the broncho-alveolar lavage fluid (BAL) were protein and albumin concentrations, angiotensin converting enzyme activity, beta-glucuronidase activity and the presence of neutrophil leucocytes. The changes observed in these variables were dose-dependent. Following exposure to 175 ppm the protein and albumin concentrations and the angiotensin converting enzyme activity showed a 100-fold increase, while the beta-glucuronidase activity showed a 10-fold increase. 5. Glucose-6-phosphate dehydrogenase and glutathione peroxidase in the supernatant of lung homogenate and gamma-glutamyl transferase activity in BAL are likely to be the most practical parameters for monitoring the phase of repair because their activities were maximal at the moment histological changes were reduced in intensity. 6. Repair was almost complete 7 d following exposure.
National Poison Control Centre, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
J
J
Meulenbelt
L
L
van Bree
J A
JA
Dormans
A B
AB
Boink
B
B
Sangster
D000280:Administration, Inhalation; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009585:Nitrogen Dioxide / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010088:Oxidoreductases; D000469:Alkaline Phosphatase; D009585:Nitrogen Dioxide