Research of the effect of mitochondria-targeted hydrogen sulfide donor AP39 treatment in an experimental allergic asthma model

In this thesis, the effect of AP39, which is a mitochondria targeted slow releasing hydrogen sulfide (H2S) donor, were investigated in a mouse model of ovalbumin (OVA)-induced allergic asthma. In this model, experimental allergic airway inflammation was induced by intranasal (i.n.) OVA administration after sensitization of mice by intraperitoneal administration of OVA. AP39 treatment was applied in these mice at doses of 250 and 1000 nmol/kg. AP39 treatment significantly prevented OVA-induced bronchial hyperreactivity in mice. OVA administration also increased lymphocyte and eosinophil cells in the bronchoalveolar lavage (BAL) fluids of mice, and these increases were inhibited by the 1000 nmol/kg dose of AP39 treatment. While higher dose of AP39 (1000 nmol/kg) treatment suppressed IL-4, IL-5 and IL-13 cytokine levels which increased in BAL, lower dose of AP39 (250 nmol/kg) had no affect on these cytokine levels. OVA-induced histopathological changes in the lung tissue were also reduced with higher dose AP39 treatment. Based on these results, AP39 reduced the occurrence of bronchial hyperreactivity and airway inflammation, which are clinical signs of allergic asthma. This is associated with the effect of hydrogen sulfide in airway smooth muscle cells to preserve mitochondrial function and therefore prevention of the allergic asthma. Further studies are needed to optimize the therapeutic efficacy of the AP39 treatment strategy including the dose and duration of the AP39 application. In conclusion, AP39, as a hydrogen sulfide donor, shows a promising therapeutic potential in respiratory diseases.