Anti-atherosclerotic Potentials of Montelukast in Chronic Ovalbumin Challenged Asthmatic Guinea Pigs Fed High Fat Diet : A Comparative Study with Fluticasone

Background: Recent evidence links the pathophysiology of asthma to cardiovascular diseases. A proatherogenic role of leukotrienes has been reported which is suggestive of a potential anti-atherosclerotic effect for leukotriene antagonists. Retrospective observations suggest that inhaled corticosteroids may reduce atherothrombotic mortality by altering systemic inflammation. Aim: the present study was designed to investigate the impact of the leukotriene antagonist montelukast on vascular dysfunctions in guinea pigs exposed to chronic ovalbumin (OVA) challenge and fed high fat diet (HFD). The potential anti-atherosclerotic effects of montelukast were compared to those of the inhaled corticosteroid fluticasone. Method: Forty-eight male guinea pigs were divided into: control non-asthmatic-chow fed (n=6), non-asthmatic-dyslipidemic; fed HFD (n=6), asthmatic-chow fed (n=18), and asthmatic-dyslipidemic groups (n=18), the last 2 groups were further subdivided into 3 groups (n=6 each): vehicle treated, montelukasttreated (10mg/kg orally) and fluticasonetreated (100μg/2ml of 0.1%ethanol PBS by inhalation) groups. Anti-asthma and Anti-atherosclerotic effects of the tested drugs were assessed. Results: Chronic OVA challenge induced atherogenic vascular changes, compared to control and potentiated the vascular dysfunctions induced by HFD in asthmatic dyslipidemic animals. Conversely, feeding animals a HFD resulted in airway inflammation and remodeling with hyper-responsiveness. Montelukast, exhibited anti-atherosclerotic effects (significant increase in % Ach-induced relaxation and phenylephrine (PhE) EC50 with reduction of PhE E-max in isolated aortic rings) of asthmatic dyslipidemic animals. These changes were associated with reduction of aortic mast cell infiltration and intima/media ratio together with a reduction in airway remodeling and mast cell infiltration. Fluticasone induced a lesser reduction in mast cell infiltration in vascular tissue as well as in the airways with lack of anti-atherosclerotic effects and reduced effects on airway remodeling. Conclusion: The anti-atherosclerotic potentials of montelukast observed implicate leukotrienes released from mast cells as possible inflammatory mediators linking asthma, obesity and atherosclerosis. The effects of montelukast may be the result of a direct effect on the vasculature as well as an indirect effect on airway remodeling through a crosstalk (involving mast cells and leukotrienes) between the airway and vascular tissue. Targeting excess leukotrienes by leukotrienes modifiers rather than by corticosteroids in dyslipidemic asthmatics might provide better control of their airway disorder as well as a reduction in the risk of atherosclerosis. [Sally Abdallah, Ahmed Abdel Salam El-Melegy, Amany Helmy Hasanin, Ghada Farouk Mohamed, Sawsan Aboul-Fotouh, Olfat Ahmed Hasan. Anti-atherosclerotic Potentials of Montelukast in Chronic Ovalbumin Challenged Asthmatic Guinea Pigs Fed High Fat Diet: A Comparative Study with Fluticasone. Life Sci J 2014;11(7):70-82]. (ISSN:1097-8135). http://www.lifesciencesite. com. 10