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

• DOI: 10.1007/s00210-012-0772-9
• Publication Date: 2013-02-15T23:19:04Z
• Authors: Manar A. Nader; Mohammed S. El-Awady; Asem A. Shalaby; Dina S. El-Agamy
• Keywords: Inflammation; Male; 0301 basic medicine; Dipeptidyl-Peptidase IV Inhibitors; Ovalbumin; Sitagliptin Phosphate; Anti-Inflammatory Agents; Nitric Oxide Synthase Type II; Triazoles; Asthma; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Pyrazines; Anti-Allergic Agents; Animals; Cytokines; Anti-Asthmatic Agents; RNA, Messenger; Bronchoalveolar Lavage Fluid; Lung

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.