Chlorphentermine-induced alterations in the lungs of vitamin E-deficient and supplemented rats:: 1. Biochemical and morphometric analysis of the pulmonary response

Male Sprague-Dawley rats were maintained on diets containing 0, 60, or 300 ppm vitamin E (VE) for 9 weeks with chlorphentermine (CP) or saline vehicle (SV) treatments administered over the last 3 weeks (20 mg CP/kg for one week and 30 mg CP/kg for subsequent 2 weeks or equivalent volume of saline vehicle). Spontaneous erythrocyte hemolysis averaged 68% for VE-deficient (0 ppm) and less than 9% for VE-supplemented (60 and 300 ppm) animals prior to saline and CP treatments. These values were not changed significantly by vehicle or drug administration. The lung-to-body weight ratios nearly doubled and the total lung phospholipid levels increased equivalently (three- to fourfold) in all three CP-treated VE groups as compared to corresponding SV controls. The levels of thiobarbituric acid-reactive material (TBA-RM), an index of lipid peroxidation, was increased in the lung tissue above SV controls in all dietary groups with the deficient group being the highest. There was no difference in the TBA-RM values of 60 and 300 ppm groups within each group. Quantitative morphometric analysis revealed that in the VE-supplemented groups, CP treatment caused a significant increase in the number of alveolar macrophage foam cells (FC) with a slight increase in the volume density of surfactant-like material (SLM). By comparison, there were fewer FCs but a larger quantity of SLM in the VE-deficient group. The results suggest that VE deficiency modifies the pulmonary response to CP resulting in lipid peroxidation-induced FC disintegration and the accumulation of SLM.