Sildenafil ve ostolün hepatoprotektif etkilerinde H2S'in rolünün araştırılması
Project no. 23603 · Status: Kapanmış · 2022
Summary
<p>High-calorie diet, alcohol, and multiple drug use increase reactive oxygen species(ROS) and cause liver damage. ROT plays a key role in the initiation and progression of liver diseases. Antioxidant therapies have beneficial effects in the management of liver diseases. Hydrogen sulfide(H2S) is a gasotransmitter involved in the regulation of vascular function,oxidative stress,glucose and lipid metabolism,many hepatic functions,including mitochondria functions. Since H2S plays role in the pathogenesis/treatment of liver diseases, it is considered a promising therapeutic target. Sildenafil is used in the treatment of pulmonary hypertension,erectile dysfunction. Osthole is a natural coumarin with antioxidant,anti-inflammatory and smooth muscle relaxant effects. Sildenafil/osthole exert their antioxidant and hepatoprotective effects by increasing antioxidants(GSH,catalase,SOD,GPx,GR),regulating Keap1/Nrf2 pathway which are common mechanisms with H2S. While the sildenafil-H2S relationship has been recently reported in the literature, it was shown for the first time in our previous project that osthole relaxes the penile tissue via H2S. The contribution of H2S to the hepatoprotective and antioxidant effects of sildenafil/osthole has not been investigated. In our project, the effects of sildenafil/osthole on endogenous H2S production in the presence/absence of oxidative stress were investigated by H2S microsensor, and the role of H2S in their antioxidant effects by chemiluminescence(luminol,lucigenin). Sildenafil/osthole increased L-cysteine-induced H2S synthesis in healthy liver and reversed the pyrogallol-induced reduction in H2S production. They decreased the pyrogallol-induced increase in ROT levels, these effects were inhibited in the presence of the H2S synthesis inhibitor aminooxyacetic acid. The H2S-mediated hepatoprotective effects of sildenafil and osthole were demonstrated for the first time in our project.</p>