THE INFLUENCE OF A DRUG-INDUCED PULMONARY LIPIDOSIS ON THE TOXICITY OF NITROGEN DIOXIDE
Abstract
This study observed the severity and duration of nitrogen dioxide (NO(,2)) toxicity on the lungs of mice after an alveolar lipidosis was induced by treatment with chlorphentermine (CP). Male Swiss-Webster mice were divided into an untreated control and three treatment groups. Treatment group I received 120 mg/kg CP daily by oral intubation for 2 weeks. Treatment group II received 20 ppm NO(,2) for 48 hr via whole-body inhalation, and treatment group III received the CP treatment prior to NO(,2) exposure. Two separate experiments were performed using these four groups. In experiment I, 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, post NO(,2) exposure. In experiment II, mice were given {methyl ('3)H}thymidine 24 hr prior to sacrifice and labeling of pulmonary cells was observed using thin-section light microscopy on days 0, 1, 3, and 5 post NO(,2) exposure. NO(,2) exposure alone caused deaths in both studies. No deaths were seen in mice that received CP prior to NO(,2). Histopathological evaluation showed slightly more type II hyperplasia and terminal bronchiolar inflammation on days 0 and 1, but noticeably less with the combination from days 3 to 7. The combination caused less terminal bronchiolar hyperplasia than NO(,2) alone on the days studied. Less edema was seen with the combination and it lasted for a shorter period. Electron microscopy supported the light microscopy results showing more type II hyperplasia and cellular response in the combination group on days 0 and 1 post NO(,2) exposure, but by day 5 type II hyperplasia was still seen in the NO(,2) alone group but not in the combination group. Autoradiography showed that CP plus NO(,2) caused significantly less loss of type I cells, less increase in type II cells, less labeling of type II cells, and less endothelial cell labeling compared to NO(,2) alone. The combination caused a significant increase in total macrophages over either individual treatment, but the labeling of these cells was less than that seen in the NO(,2) alone group after the first day post NO(,2) exposure. The results indicated that CP-induced lipoproteinosis offered a protection against the lethal effects of a 48-hr 20 ppm NO(,2) exposure, and that the cellular repair mechanism was concluded at an earlier time.
Degree
Ph.D.
Subject Area
Environmental science
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