One-electron reduction triggered nitric oxide release for ischemia-reperfusion protection

Xiu Xu; Meiling Sun; Xiao Luo; Ziqian Zhang; Lin Su; Lingfei Cui; Zhihui Zhu; Xicun Lu; Rui Wang; Feng Han; Xuhong Qian; Youjun Yang

doi:10.1016/j.freeradbiomed.2020.12.443

One-electron reduction triggered nitric oxide release for ischemia-reperfusion protection

Free Radic Biol Med. 2021 Feb 20:164:13-19. doi: 10.1016/j.freeradbiomed.2020.12.443. Epub 2021 Jan 5.

Authors

Xiu Xu¹, Meiling Sun², Xiao Luo³, Ziqian Zhang⁴, Lin Su¹, Lingfei Cui⁵, Zhihui Zhu², Xicun Lu¹, Rui Wang¹, Feng Han⁶, Xuhong Qian¹, Youjun Yang⁷

Affiliations

¹ State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
² Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
³ School of Chemistry and Molecular Engineering, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
⁴ Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, 530200, China.
⁵ School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China.
⁶ Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. Electronic address: [email protected].
⁷ State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China. Electronic address: [email protected].

PMID: 33418107
DOI: 10.1016/j.freeradbiomed.2020.12.443

Abstract

Nitric oxide donors (NODs) are indispensable in biological research and disease treatment. NODs had been utilized to treat cardiovascular diseases in clinic and many others are under trial. Thiols are typically required for these donors to release NO. Yet, their mechanism is complex and often lead to resistance. Herein, we reported that N-nitrosated electron-deficient dyes are capable of NO release with one-electron reduction. A fluorophore is generated simultaneously, whose fluorescence is harnessed to monitor the profile of NO release. Through electrochemical and spectral studies, NOD f3 was found to exhibit good biocompatibility and high reduction efficiency and its potentials in cell-protection in oxygen and glucose deprivation (OGD) models were showcased with endothelial cells. This work aims at offering a new approach to design reduction-triggered NOD, which have therapeutic potentials in ischemia-reperfusion.

Keywords: Fluorescence; Ischemia-reperfusion protection; N-nitrosated dye; Nitric oxide; Reduction-triggered release.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Electrons
Endothelial Cells
Humans
Ischemia
Nitric Oxide*
Reperfusion
Reperfusion Injury* / prevention & control

Substances

Nitric Oxide