Hydrogen sulfide:a novel mechanism for the vascular protection by resveratrol under oxidative stress in mouse aorta

Reactive oxygen species (ROS) decreases bioavailability of nitric oxide (NO) and impairs NO-dependent relaxations. Like NO, hydrogen sulfide (H2S) is an antioxidant and vasodilator; however, the effect of ROS on H2S-induced relaxations is unknown. Here we investigated whether ROS altered the effect of H2S on vascular tone in mouse aorta and determined whether resveratrol (RVT) protects it via H2S. Pyrogallol induced ROS formation. It also decreased H2S formation and relaxation induced by l-cysteine and in mouse aorta. Pyrogallol did not alter sodium hydrogensulfide (NaHS)-induced relaxation suggesting that the pyrogallol effect on l-cysteine relaxations was due to endogenous H2S formation. RVT inhibited ROS formation, enhanced l-cysteine-induced relaxations and increased H2S level in aortas exposed to pyrogallol suggesting that RVT protects against "H2S-dysfunctions" by inducing H2S formation. Indeed, H2S synthesis inhibitor AOAA inhibited the protective effects of RVT. RVT had no effect on Ach-induced relaxation that is NO dependent and the stimulatory effect of RVT on H2S-dependent relaxation was also independent of NO. These results demonstrate that oxidative stress impairs endogenous H2S-induced relaxations and RVT offers protection by inducing H2S suggesting that targeting endogenous H2S pathway may prevent vascular dysfunctions associated by oxidative stress

Drug Repurposing in the Treatment of COVID-19

Yetik Anacak, Gunay/0000-0002-7788-1657WOS:000613758900005The use of drugs that have been previously defined for certain indications in new indications is defined as the repurposing/repositioning of the drug. The requirement of all clinical research steps that starts from healthy volunteers, due to the slowness of new drug discovery, longer time to reach the market, and high cost to develop a new drug, make drug repurposing an attractive pharmacoeconomic solution. Repositioning of drugs becomes even more important, especially in situations where time is vital and emergency in drug development such as pandemics. in this review, we have both summarized the techniques used for drug repositioning and evaluated drugs that have been repositioned in Coronavirus Disease (COVID-19) treatment based on three main strategies, target-disease and drug-based. Considering the availability of the results of pharmacovigilance studies and long-term toxic effects of old drugs provide an important advantage compared to traditional drug discovery in COVID-19 treatment, where sepsis and multi-organ dysfunction can occur

The role of eNOS on the compensatory regulation of vascular tonus by H2S in mouse carotid arteries

WOS: 000408396500006PubMed ID: 28414104The gasotransmitter nitric oxide (NO) has an important role in vascular function and a decrease in its bioavailability is accepted as a main pathological mechanism for cardiovascular diseases. However, other gasotransmitters such as hydrogen sulfide (H2S) are also generated by the endothelium and can also affect vascular tone and a crosstalk may exist between H2S and NO. We therefore investigated the consequences of deficiency, replacement or overexpression of endothelial nitric oxide synthase (eNOS) on H2S-induced vascular responses in murine carotid arteries. In pre-contracted carotid arteries from wild-type (WT) mice, L-cysteine elicited relaxation that was inhibited by the H2S synthesis inhibitor amino-oxyacetic acid (AOAA). Genetic deletion of eNOS increased L-cysteine-induced relaxation compared to WT, but the replacement of eNOS by adenoviral transfection or H2S synthesis inhibition by AOAA reversed it. Furthermore, eNOS deletion did not alter NaHS-induced relaxation in carotid arteries while eNOS overexpression/replacement increased NaHS-induced relaxation responses in carotid arteries from WT or eNOS(-/-). We suggest that, endogenously produced H2S can compensate for impaired vasodilatory responses in the absence of NO to maintain vascular patency; while, eNOS abundance can limit endogenous H2S-induced vascular responses in mice carotid arteries. Our result suggests that endogenous vs. exogenous H2S-induced relaxation are reciprocally regulated by NO in mice carotid arteries. (C) 2017 Elsevier Inc. All rights reserved.TUBITAK (The Scientific and Technological Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109s453]; STSMThis study was supported by TUBITAK (The Scientific and Technological Research Council of Turkey) grant # 109s453 (GYA) allowing to joining COST action BM1005. The MC members (GYA and IF) thank COST action BM1005 for networking and the support by a STSM (EE)

Hydrogen sulfide is involved in the antioxidant effects of taurine

3rd European Conference on the Biology of Hydrogen Sulfide (H2S) -- MAY 03-06, 2015 -- Athens, GREECEWOS: 00035331390012

The role of hydrogen sulfide on the regulation of vascular tonus in mice aorta and relation with taurine

3rd European Conference on the Biology of Hydrogen Sulfide (H2S) -- MAY 03-06, 2015 -- Athens, GREECEWOS: 00035331390012

Investigation of changes in vWF expression in rabbit carotid artery collar model

WOS: 000430370600006Objective: Placement of a soft silicone collar around the carotid arteries of rabbits induces intimal thickening which is considered as one of the crucial steps in the development of atherosclerosis. In this study we aimed to investigate vWF expression levels on days 7 and 14 after collar placement.& para;& para;Methods: A soft inert silicon collar was placed around the left carotid artery for 7 and 14 days. vWF expression was investigated by quantitave RT-PCR. In each artery (collar or sham) cross-sectional areas of intima, media were measured and intima/ media ratio was calculated.& para;& para;Results: Intimal thickening was more pronounced on day 14 compared to day 7. However the collar caused increase in vWF expression which was found to be at the same level on days 7 and 14.& para;& para;Conclusion: Our findings emphasize the importance of vWF in collar-induced intimal thickening