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不同造血干细胞供体作为血管舒张剂和超氧化物诱导的内皮损伤减弱剂的比较研究

Comparative Study of Different HS Donors as Vasodilators and Attenuators of Superoxide-Induced Endothelial Damage.

作者信息

Marini Elisabetta, Rolando Barbara, Sodano Federica, Blua Federica, Concina Giulia, Guglielmo Stefano, Lazzarato Loretta, Chegaev Konstantin

机构信息

Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy.

Department of Pharmacy, "Federico II" University of Naples, 80131 Naples, Italy.

出版信息

Antioxidants (Basel). 2023 Feb 1;12(2):344. doi: 10.3390/antiox12020344.

Abstract

In the last years, research proofs have confirmed that hydrogen sulfide (HS) plays an important role in various physio-pathological processes, such as oxidation, inflammation, neurophysiology, and cardiovascular protection; in particular, the protective effects of HS in cardiovascular diseases were demonstrated. The interest in HS-donating molecules as tools for biological and pharmacological studies has grown, together with the understanding of HS importance. Here we performed a comparative study of a series of HS donor molecules with different chemical scaffolds and HS release mechanisms. The compounds were tested in human serum for their stability and ability to generate HS. Their vasorelaxant properties were studied on rat aorta strips, and the capacity of the selected compounds to protect NO-dependent endothelium reactivity in an acute oxidative stress model was tested. HS donors showed different HS-releasing kinetic and produced amounts and vasodilating profiles; in particular, compound was able to attenuate the dysfunction of relaxation induced by pyrogallol exposure, showing endothelial protective effects. These results may represent a useful basis for the rational development of promising HS-releasing agents also conjugated with other pharmacophores.

摘要

在过去几年中,研究证据证实硫化氢(HS)在各种生理病理过程中发挥着重要作用,如氧化、炎症、神经生理学和心血管保护;特别是,HS在心血管疾病中的保护作用得到了证实。随着对HS重要性的认识不断加深,作为生物学和药理学研究工具的HS供体分子也越来越受到关注。在此,我们对一系列具有不同化学结构和HS释放机制的HS供体分子进行了比较研究。这些化合物在人血清中测试了其稳定性和产生HS的能力。在大鼠主动脉条上研究了它们的血管舒张特性,并测试了所选化合物在急性氧化应激模型中保护NO依赖性内皮反应性的能力。HS供体表现出不同的HS释放动力学、产生量和血管舒张谱;特别是,化合物能够减轻焦性没食子酸暴露诱导的舒张功能障碍,显示出内皮保护作用。这些结果可能为合理开发与其他药效基团共轭的有前景的HS释放剂提供有用的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b56e/9951978/84de4363a8ba/antioxidants-12-00344-g001.jpg

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