ABSTRACT
Dugs used currently to treat asthma have limitations partly due to their undesired effects. PPARgamma agonists including rosiglitazone may offer additional therapeutic advantages to current treatment. The aim of the present study was to assess the anti-inflammatory potential of a PPARi agonist, rosiglitazone, locally delivered by means of nebulization in a guinea pig model of asthma, in comparison with that of the corticosteroid budesonide. Five groups of guinea pigs were used, five animals each. The first group was Sham -sensitized guinea pigs; the other four groups were sensitized by ovalbumin [OVA] by allergen solution containing 100 micrograms OVA and 100 mg Al [OH]3 per ml saline. 0.5 ml was injected intraperitoneally, while another 0.5 ml of the solution was divided over seven intracutaneous injection sites. The second group was OVA-sensitized and exposed to inhalation of saline. The third, fourth and fifth group were OVA albumin-sensetized. The third group was treated with vehicle inhalation, The fourth group was treated with rosiglitazone and the fifth group was treated with budesonide. Animals in the last 3 groups were exposed to allergen provocation procedure [Ag challenge] from weeks 4 to 5 after OVA sensitization. Assessment of asthma was done by studying the effect of rosiglitazone and budesonide on airway hyper responsiveness [AHR] to acetylcholine [Ach], inflammatory cellular changes in bronchoalveolar lavage and histopathological changes. The effect of rosiglitazone and budesonide pretreatment on histamine induced contraction of isolated OVA sensitized guinea pig tracheal spiral strips was also investigated. In addition, the direct effect of rosiglitazone and budesonide incubation on histamine induced contraction of isolated guinea pig tracheal spiral strips was examined. The results revealed that one week pre-treatment with rosiglitazone [20 minutes inhalation in a dose of 300 microg/ Kg/ day] and budesonide [20 minutes inhalation in a dose of 2mg/ Kg/ day] resulted in significant reduction in airway hyperreactivity to inhaled Ach, inflammatory cellular content in bronchoalveolar lavage fluid [BALF] and improvement in histopathological changes of asthmatic lung. There was no significant difference between both drugs as regard improvement of AHR, reduction in thickness of the interalveolar septum, decrease in total leucocytic count [TLC], count of lymphocytes and macrophages. However, budesonide caused significant reduction in eosinophils and macrophages count in comparison to rosiglitazone. In addition, rosiglitazone had a direct relaxant effect on airway smooth muscle. The results provided evidence for the therapeutic potential of inhaled PPARi agonist, rosiglitazone, in the treatment of airway asthmatic inflammation. In addition PPARgamma agonists had a direct relaxant effect on the isolated tracheal smooth muscle