The Effect of Chlorphentermine Pretreatment on the Toxicity of Nitrogen Dioxide in Mice

• Published in: Toxicological sciences Vol. 9; no. 1; pp. 69 - 81
• Main Authors: HASTINGS, CHARLES E., DENICOLA, DENNIS B., REBAR, ALAN H., TUREK, JOHN J., BORN, GORDON S., KESSLER, WAYNE V.
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.07.1987
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/9.1.69

The Effect of Chlorphentermine Pretreatment on the Toxicity of Nitrogen Dioxide in Mice. HASTINGS, C. E., JR., DENICOLA, D. B., REBAR, A. H., TUREK, J. J., BORN, G. S., AND KESSLER, W. V. (1987). Fundam. Appl Toxicol 9, 69–81. Chlorphentermine HCl (CP) was used to induce preexisting alveolar alterations resembling a pulmonary lipidosis in mice to study these effects on the severity and duration of nitrogen dioxide (NO2) toxicity. Results indicated that a daily dose of 120 mg/kg for 14 days produced consistent histopathologic changes characterized by an accumulation of large foamy macrophages. Male Swiss-Webster mice were divided into a control and three treatment groups. Group 1 received 120 mg/kg CP po daily for 2 weeks followed by exposure to air for 48 hr. Group 2 received 20 ppm NO2 for 48 hr via whole-body inhalation, and group 3 received 120 mg/kg CP daily for 2 weeks followed by 20 ppm NO2 for 48 hr. The fourth group served as a nontreated control and received water in place of CP and air in place of NO2. All groups were compared by morphologic evaluation of pulmonary tissues at the light and electron microscopic levels at Days 0, 1, 3, 5, and 7 after the 48-hr exposure to air or NO2. In a second experiment using the same treatment groups, thin-section light microscopy was used to count the number of type I and type II cells and macrophages. NO2 exposure alone caused deaths in 20.8 and 18.5% of the mice in the two studies, but no deaths were seen in the combination groups from both experiments. Histopathologic evaluation showed a typical cellular response to the NO2 exposure, but differences were noted between the two groups receiving NO2 on this treatment. There was increased type II cell hyperplasia and terminal bronchiolitis on Days 0 and 1 but less on Days 3 to 7 in the combination group compared to the NO2 alone group. CP treatment prior to NO2 exposure caused less terminal bronchiolar epithelial hyperplasia and less pulmonary edema than was seen in the NO2 along group. The CP treatment appeared to protect against the lethal effects of NO2 at the concentration and time of exposure used and altered the cellular repair mechanism that occurs in response to NO2 toxicity. CP treatment prior to NO2 exposure caused significantly less loss of type I cells and less increase in type II cells due to NO2 damage. The combination treatment also caused an increase in macro phages greater than that seen in either individual treatment, and this number remained increased through 5 days post-NO2 exposure, whereas the NO2 alone caused a steady increase in macro phages following the exposure until Day 3. Overall, prior treatment with CP offered partial protection against NO2 toxicity.