Effect of a mucoactive compound (CO 1408) on airway hyperreactivity and inflammation induced by passive cigarette smoke exposure in guinea-pigs.
Environmental exposure to tobacco smoke contributes to the onset of several lung diseases, e.g. chronic bronchitis and asthma, including an increase in airway reactivity. We have investigated the effect of a new mucoactive compound, CO 1408, on airway hyperreactivity and lung inflammation induced in guinea-pigs by passive cigarette smoke exposure. Animals were exposed to cigarette smoke in a Plexi-glass box, three times a day for four days. Airway reactivity to histamine was assessed ex-vivo in lung parenchymal strips. As a measure of lung inflammation, the number of leucocytes was evaluated in bronchoalveolar lavage (BAL) fluids and histological sections. Passive smoke exposure potentiated histamine-induced contraction in lung parenchymal strips, a phenomenon associated with an increase in proinflammatory cells in the BAL fluids and enhanced eosinophil infiltration into parenchymal tissues. Pretreatment with oral CO 1408 at 400 mg.kg-1 but not 100 mg.kg-1, completely prevented the cigarette smoke-induced airway hyperreactivity. 400 mg.kg-1 CO 1408 also inhibited the increase in cell numbers in the BAL fluids, but not eosinophil recruitment in parenchymal tissues. The present data indicate the ability of CO 1408 to modulate smoke-induced airway hyperreactivity and, to some extent, lung inflammation, an effect which might be of value in the therapy of obstructive pulmonary diseases.
Hernandez
A
A
Institute of Pharmacological Sciences, University of Milan, Italy.
Daffonchio
L
L
Brandolini
L
L
Zuccari
G
G
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D003511:Cyclohexanols / Q000494:pharmacology*; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D014028:Tobacco Smoke Pollution
D003511:Cyclohexanols; D053138:Cyclohexenes; D014028:Tobacco Smoke Pollution; C065237:6-hydroxy-4-(1-hydroxy-1-methylethyl)-1-cyclohexene-1-ethanol; D006632:Histamine