[Effect of phosphodiestrase 4 inhibitor (rolipram) on experimental allergic asthma-guinea pig model].
Selective phosphodiesterases (PDE) inhibitors are the new group of antiasthmatic drugs, which integrate antiinflammatory activity with bronchoconstriction counteraction. Selective inhibitors of phosphodiesterase type 4 are used as alternative or assist drugs in treatment of respiratory system diseases. So far glucocorticosteroids remain the most efficient and widely used medicine in the treatment of asthma. However application of glucocorticosteroid is greatly limited because of numerous side effects, what induce to permanent search for new antiasthmatic drugs. Examination new substances are executed on animal models. Guinea pig model is widely used to research course of asthmatic reaction. This model is especially convenient on the ground of that: lung is major shock organ, airway respond to histamine, animals demonstrated early asthmatic reaction (EAR) and late asthmatic reaction (LAR), eosinophils flow in bronchoalveolar space during LAR. In ovalbumin (OA) sensitized guinea pigs hypersensitivity reaction breaks out as a result of OA provocation. Aims of our experiments, execute on guinea pig model were to determine the influence of rolipram (PDE 4 inhibitor) on modulation experimental asthmatic reaction and comparison activity of rolipram versus dexamethasone in attribution to chosen parameters of allergic reaction such as: lung resistance, influx of protein and inflammatory cells in airways, and mastocytes degranulation. Experiments were made on guinea pigs sensitized and provoked with ovalbumin The obtain data indicate that rolipram was effective in reduction the rise of lung resistance during EAR, restricted influx of eosinophils to bronchoalveolar space between 1,5 and 24 hours after provocation, and reduced increase of histamine concentration in bronchoalveolar lavage fluid (BALf). Rolipram had no influence on number of neutrophils present in BALf. Dexamethasone in double dose of 1,2mg/kg effectively bordered the growth of lung resistance during EAR, and broke influx of eosinophils and neutrophils to bronchoalveolar space.
Nejman-Gryz
Patrycja
P
Katedra i Klinika Chorób Wewnetrznych, Pneumonologii i Alergologii, AM, Warszawa. patrycja@amwaw.edu.pl
Grubek-Jaworska
Hanna
H
Glapińiski
Jarosław
J
Chazan
Ryszarda
R
D000280:Administration, Inhalation; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006636:Histamine Release / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000737:chemistry; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D020889:Rolipram / Q000627:therapeutic use*
D000485:Allergens; D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D003907:Dexamethasone; D010047:Ovalbumin; D020889:Rolipram