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Characterization and Biological Activity of a Hydrogen Sulfide-Releasing Red Light-Activated Ruthenium(II) Complex.

ABSTRACT: Hydrogen sulfide (H2S) is a biological gasotransmitter that has been employed for the treatment of ischemia-reperfusion injury. Despite its therapeutic value, the implementation of this gaseous molecule for this purpose has required H2S-releasing prodrugs for effective intracellular delivery. The majority of these prodrugs, however, spontaneously release H2S via uncontrolled hydrolysis. Here, we describe a Ru(II)-based H2S-releasing agent that can be activated selectively by red light irradiation. This compound operates in living cells, increasing intracellular H2S concentration only upon irradiation with red light. Furthermore, the red light irradiation of this compound protects H9c2 cardiomyoblasts from an in vitro model of ischemia-reperfusion injury. These results validate the use of red light-activated H2S-releasing agents as valuable tools for studying the biology and therapeutic utility of this gasotransmitter.

SUBMITTER: Woods JJ

PROVIDER: S-EPMC6599746 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Characterization and Biological Activity of a Hydrogen Sulfide-Releasing Red Light-Activated Ruthenium(II) Complex.

Woods Joshua J JJ Cao Jian J Lippert Alexander R AR Wilson Justin J JJ

Journal of the American Chemical Society 20180919 39

Hydrogen sulfide (H2S) is a biological gasotransmitter that has been employed for the treatment of ischemia-reperfusion injury. Despite its therapeutic value, the implementation of this gaseous molecule for this purpose has required H2S-releasing prodrugs for effective intracellular delivery. The majority of these prodrugs, however, spontaneously release H2S via uncontrolled hydrolysis. Here, we describe a Ru(II)-based H2S-releasing agent that can be a ...[more]

PMID: 30230336

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Project description:By electrospinning of polycaprolactone (PCL) solutions containing N-(benzoylthio)benzamide (NSHD1), a H2S donor, fibrous scaffolds with hydrogen sulfide (H2S) releasing capability (H2S-fibers) are fabricated. The resultant microfibers are capable of releasing H2S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H2S release peaks of H2S-fibers appeared at 2-4h, while the peak of donor alone showed at 45 min. H2S release half-lives of H2S-fibers were 10-20 times longer than that of donor alone. Furthermore, H2S-fibers can protect cells from H2O2 induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H2S-fibers application as a wound dressing in vitro. Given that H2S has a broad range of physiological functions, H2S-fibers hold great potential for various biomedical applications.Statement of significanceHydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H2S suggests H2S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H2S donors have been developed and applied for biomedical studies, most of H2S donors have the shortage that the H2S release is either too fast or uncontrollable, which poorly mimic the biological generation of H2S. By simply combining electrospinning technique with our designed biological thiols activated H2S donor, NSHD1, we fabricated H2S releasing microfibers (H2S-fibers). This H2S-fibers significantly prolonged the releasing time compared to H2S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H2S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H2S releasing capacity. We anticipate this H2S-releasing scaffold will have great potential for biomedical applications.

Dataset Information

Characterization and Biological Activity of a Hydrogen Sulfide-Releasing Red Light-Activated Ruthenium(II) Complex.

Publications

Characterization and Biological Activity of a Hydrogen Sulfide-Releasing Red Light-Activated Ruthenium(II) Complex.

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