Exploration of a novel adjuvant therapeutic regimen using a potent glucocorticoid receptor agonist along with iNOS inhibitor in murine model of asthma

Abstract

Allergic asthma is mainly characterized by allergen-induced IAR (immediate airway response) and LAR (late airway response). In regards to the results of lung tissue histology and bronchoalveolar lavage fluid analysis, it was confirmed that there is the existence of a casual relationship of eosinophil and other inflammatory cell infiltration in bronchial sub-mucosa in the mechanism of LAR. This investigation aimed to examine the anti-asthmatic effect of novel adjuvant therapeutic regimens using a low dose of potent glucocorticoid receptor agonist i.e., Dexamethasone, along with iNOS inhibitor i.e., Aminoguanidine in a both acute and chronic murine model of asthma. Female BALB/c mice of 8 weeks of age were taken and divided into 6 experimental groups i.e. normal control, OVA control, aminoguanidine (200mg/kg), combination of aminoguanidine (200mg/kg) along with dexamethasone (0.03mg/kg), low dose dexamethasone (0.03mg/kg) and Dexamethasone (0.1mg/kg) treated group. After sensitization and introduction of drugs, mice were sacrificed by cervical dislocation and bronchoalveolar lavage (BAL) fluid analyzed. The result of this study stated that there is a significant reduction in the levels of inflammatory cytokines in combination-treated animals with respect to alone dexamethasone, which may be due to the synergistic effect of aminoguanidine and dexamethasone. From histopathological evidence, it can be concluded that combination treatment having a better lung adaptation mechanism and can improve the condition aggressively. The findings of the study throw some light on an additive therapeutic regimen of aminoguanidine can have a better impact with glucocorticoids.