IMPACT OF HIGH FAT DIET ON ASTHMATIC RESPONSE AND ON ANTI-ASTHMA EFFECTS OF MONTELUKAST AND FLUTICASONE IN CHRONICALLY OVALBUMIN CHALLENGED GUINEA PIGS
Sally Abdallah , Amany Helmy , Sawsan Aboul-Fotouh , Ghada Farouk Mohamed* , Ahmed Abdel Salam El-Melegy , Olfat Ahmed Hasan
Department of Pharmacology, *Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Background: It is increasingly recognized that obese people are more prone to develop asthma, with increased severity among those in the overweight and obese groups. Some evidences suggested that obesity might alter the efficacy of antiasthma medication. Aim: The present study was designed to investigate the impact of high fat diet (HFD) on the asthmatic response to chronic Ovalbumin (OVA) challenge and on the anti-asthma effects of the leukotriene antagonist montelukast and the inhaled corticosteroid fluticasone. Method: Forty eight male guinea pigs were divided into: control non-asthmatic chow-fed (n=6), non-asthmatic-HFD (n=6), asthmatic-chow fed (n=18), and asthmatic-HFD groups (n=18), the last 2 groups were further subdivided into 3 groups (n=6 each): vehicle treated, montelukast- treated (10mg/kg orally) and fluticasone-treated (100µg/2ml of 0.1%ethanol PBS by inhalation) groups. Animals were assessed for metabolic and airway dysfunctions. Results: Feeding animals a HFD with chronic OVA challenge resulted in metabolic changes, increase in airway hyper-responsiveness, total leucocytic count and % of neutrophils in broncho-alveolar lavage as well as lung mast cells infiltration and airway remodeling. Montelukast reduced airway hyper-responsiveness in both asthmatic-chow fed and asthmatic-HFD animals. In contrast fluticasone reduced airway hyper-responsiveness in the asthmatic–chow fed group only. Montelukast exhibited more anti-remodeling effect and greater reduction in mast cell and neutrophil infiltration in the airways of the asthmatic-HFD group compared to fluticasone. Conclusion: Dyslipidemic metabolic changes as well as increase in mast cell and neutrophil infiltration induced by feeding animals a HFD might be involved in induction of asthmatic airway changes. The greater reduction in mast cell and neutrophil infiltration by montelukast compared to fluticasone with subsequent greater anti-remodeling effect might explain its more pronounced anti-asthma effects in asthmatic-HFD animals. The greater anti-asthma effects of the leukotriene antagonist montelukast, compared to fluticasone, in asthmatic-HFD animals emphasizes the key role played by mast cells and inflammatory leukotrienes in the underlying pathological processes contributing to both asthma and obesity. Targeting leukotrienes and perhaps other mast cell inflammatory mediators might prove to be better alternative control medications than steroids for managing asthma in obese patients or in those with the metabolic syndrome.