Sitagliptin exerts anti-inflammatory and anti-allergic effects in ovalbumin-induced murine model of allergic airway disease

Abstract

Sitagliptin, a new oral glucose lowering medication, is used for treatment of type 2 diabetes mellitus. The anti-inflammatory property of sitagliptin is reported, yet no studies have been done on asthma. In the present study, the effect of sitagliptin on allergic asthma was investigated using ovalbumin (OVA)-induced asthma model in mice. Swiss male albino mice sensitized and challenged to ovalbumin were treated with sitagliptin (8 mg/kg administered orally twice a day). Drug treatment was done on each day from days 16 to 23, 1 h before the challenge on the days of challenge. Sitagliptin treatment markedly decreased inflammatory cell accumulation in bronchoalveolar lavage (BAL) fluid and in the lungs, as revealed by histopathological examination. Furthermore, the levels of interleukin (IL)-13 in BAL fluid, total and OVA specific immunoglobulins (Ig)-E in serum, were significantly reduced as compared to the OVA group. In addition, sitagliptin significantly increased superoxidase dismutase (SOD) and reduced glutathione (GSH) activities with significant decrease in malondialdehyde (MDA) content in the lung. Importantly, sitagliptin decreased mRNA expression of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and transforming growth factor-β(1) (TGF-β(1)) in lung tissues as compared to the OVA group. Moreover, nitric oxide content as well as the mRNA expression of inducible nitric oxide synthase (iNOS) was remarkably decreased by sitagliptin treatment. Sitagliptin attenuates the allergic airway inflammation suggesting that sitagliptin may have applications in the treatment of bronchial asthma.

Inhibition of airway inflammation and remodeling by sitagliptin in murine chronic asthma

“…For dexamethasone, this was in agreement with the reports of Reber et al [24] and Herbert et al [25] who demonstrated that after short-or long-term therapy with dexamethasone there was a reduction in the total number of cells and eosinophils in BAL fluid in murine model of asthma. Also it was previously reported by Nader et al [16] that sitagliptin-treated mice had significantly reduced lung eosinophilia in BAL fluid and lung tissue as compared to OVA challenged mice in acute allergic asthma. The relationship between airway inflammation and airway remodeling was found to be complex.…”

“…Moreover, sitagliptin inhibited immediate-type hypersensitivity allergic reaction through inhibition of histamine release and proinflammatory cytokine production in rat peritoneal mast cells [15]. It has been demonstrated in an acute murine model of bronchial asthma that sitagliptin can enhance antioxidant status and downregulate some inflammatory cytokines expression through exerting antiinflammatory/immunomodulatory activities [16]. In this study, using a chronic model of allergic airway inflammation with subepithelial fibrosis, the effect of sitagliptin on underlying mechanisms potentially involved in airway inflammation and remodeling was investigated.…”

Comparative Study of the Protective Effect of Metformin and Sitagliptin against Doxorubicin-Induced Cardiotoxicity in Rats

“…Cardio protective effect of sitagliptin may be due to reduction in inflammatory markers by down-regulation of COX-2 expression [47] and iNOS expression [48], decreasing free radicals [49] and nitro oxidative stress parameters (MDA and NOx) by increase SOD activity [50].…”

Sitagliptin Impairs Healing of Experimentally Induced Gastric Ulcers via Inhibition of Inos and Cox-2 Expression

“…Nader et al (2012) have shown that NO content as well as the mRNA expression of iNOS was remarkably decreased by sitagliptin treatment in murine model of allergic airway disease.…”