1992 Volume 30 Issue 4 Pages 585-592
Elastolytic enzymes and active oxygen species derived from leukocytes and alveolar macrophages during exposure to tobacco smoke, together with active oxygen species directly derived from tobacco smoke, are thought to play a crucial role in the pathogenesis of pulmonary emphysema by inactivating α1 protease inhibitor (α1PI), a novel anti-elastase. We studied the inhibitory effect of probucol, an oral hypocholesterolemic agent, on tobacco smokeinduced decrease in plasma anti-elastase activity (EIA) and ferroxidase activity (FA) in conscious venous catheter instrumented rats.
Rats exposed to the smoke of 5 cigarettes (nicotine 11mg, tar 115mg) in a plastic chamber showed a prompt increase in plasma COHb to 17.9±2.7%, and a prompt decrease in plasma EIA by -17.9% (p<0.05) and FA by -14.8% (p<0.01), which lasted for 6 hours after exposure. Rats administered probucol (1% probucol in food) for 3 days showed normocholesterol plasma levels, and rats administered probucol for 4 weeks showed hypocholesterolemic plasma levels. EIA and FA were not depressed after smoking, and lipid peroxide product (TBA reactive substance) in lung tissue (p<0.05) and serum (p<0.1) showed a smaller increase in association with a smaller decrease in the ratio of lung tissue GSH/GSSG (p<0.01) compared with control rats.
These results indicate that probucol, via its antioxidant action rather than its cholesterol lowering effect, has a protective effect on lung exposed to tobacco smoke in terms of protease-antiprotease balance and oxidantantioxidant balance.
