[Probucol inhibits tobacco smoke-induced decrease in plasma anti-elastase activity and ferroxidase activity in rats].
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 alpha 1 protease inhibitor (alpha 1 PI), a novel anti-elastase. We studied the inhibitory effect of probucol, an oral hypocholesterolemic agent, on tobacco smoke-induced 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 11 mg, tar 115 mg) 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 less than 0.05) and FA by -14.8% (p less than 0.01), which lasted for 6 hours after exposure. Rats administered probucol (1% probucol in food) for 3 days showed normal cholesterol 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 less than 0.05) and serum (p less than 0.1) showed a smaller increase in association with a smaller decrease in the ratio of lung tissue GSH/GSSG (p less than 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 oxidant-antioxidant balance.
Kishi
Y
Y
Department of Internal Medicine, Fukui Medical School, Japan.
Ishizaki
T
T
Sasaki
F
F
Takahashi
H
H
Ameshima
S
S
Nakai
T
T
Miyabo
S
S
D000818:Animals; D002570:Ceruloplasmin / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000097:blood; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012907:Smoking / Q000009:adverse effects*
D002570:Ceruloplasmin; D010196:Pancreatic Elastase; D005978:Glutathione; D011341:Probucol