EFFECTS OF CHLORPHENTERMINE AND NITROGEN DIOXIDE ON THE MURINE ALVEOLAR MACROPHAGE (LIPIDOSIS, LIPOPEROXIDATION)
Abstract
An LC50 study was performed to examine the effect of chlorphentermine (CP) on nitrogen dioxide (NO(,2)) toxicity. Male Swiss-Webster mice were tested by gavage with CP (120 mg/kg daily for 2 weeks) or an equal volume of H(,2)O (daily for 2 weeks). These mice were then exposed to 20, 30, 40, 50, or 60 ppm NO(,2) for 48 hr by whole-body inhalation. Mortality was observed immediately following each exposure. No significant difference was seen between the LC50's of the H(,2)O/NO(,2) and CP/NO(,2) groups, the LC50's of both groups falling between 40 and 50 ppm. The only apparent difference was in the mortalities for the H(,2)O- and CP-treated groups exposed to 50 ppm NO(,2) for 48 hr, which were 90.0 and 61.5%, respectively. Functional changes of alveolar macrophages (MP) following CP and NO(,2), alone or in combination, were then examined. MP's were collected by bronchoalveolar lavage from mice treated as those in the LC50 study (H(,2)O/NO(,2) and CP/NO(,2)). In addition, MP's were collected from mice that were treated with either H(,2)O or CP and then exposed to compressed air (CA), the H(,2)O/CA group being the control group. Function studies included nitroblue tetrazolium dye reduction, 5'-nucleotidase activity, and yeast phagocytosis and killing assays. These assays were performed on viable, pure adherent MP populations. The 5'-nucleotidase activity and yeast phagocytosis and killing assays suggested that CP increased phagocytosis. The percentage metabolic reduction and microbicidal killing following CP tended to be depressed when compared to controls, but absolute reduction and killing (percentage values times total MP's) appeared to be greatly increased following these treatments. The increased functions appeared to be highly dependent on the increase in the total number of MP's induced by CP and may be important in the repair mechanism following NO(,2) damage. The results suggest that a major component of the protection mechanism against NO(,2) toxicity in the lipidotic lung is the large accumulation of MP's in the airways. NO(,2) may interact with the MP membranes, accumulated lipids, and activated reduction system (e.g., glutathione antioxidant system) leading to the quenching of the free radicals formed by NO(,2)-induced lipid peroxidation.
Degree
Ph.D.
Subject Area
Pharmacology
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