Edoxaban Exerts Antioxidant Effects Through FXa Inhibition and Direct Radical-Scavenging Activity
Abstract
:1. Introduction
2. Results
2.1. Effect of Edoxaban on Intracellular Reactive Oxygen Species Production Induced by FXa in HK-2 Cells
2.2. Effect of Edoxaban on Intracellular Reactive Oxygen Species Production Induced by Indoxyl Sulfate and Angiotensin II in HK-2 Cells
2.3. Radical Scavenging Activity of Edoxaban Against Hydroxyl Radical and Hydrogen Peroxide Decomposition Ability
2.4. Radical Scavenging Activity of Edoxaban against Peroxynitrite
2.5. Radical Scavenging Activity of Edoxaban against Superoxide Radical
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Cell Culture
4.3. Measurement of Reactive Oxygen Species Production
4.4. Electron Spin Resonance Spectroscopy
4.5. Measurement of Hydrogen Peroxide Decomposition
4.6. Peroxynitrite Scavenging Assay Using Dihydrorhodamine123
4.7. Statistical Analysis
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AII | Angiotensin II |
CKD | Chronic kidney disease |
CM-H2DCFDA | Chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate |
Ccr | Creatinine clearance |
DMEM | Dulbecco’s modified Eagle’s medium |
DMPO | Dimethyl-1-pyrroline-N-oxide |
DHR123 | Dihydrorhodamine123 |
D-PBS | Dulbecco’s phosphate buffered saline |
DPI | Diphenyleneiodonium chloride |
ESR | Electron spin resonance |
FXa | Factor Xa |
H2O2 | Hydrogen peroxide |
HK-2 cells | Human proximal tubular cells |
IS | Indoxyl sulfate |
NADPH | Nicotinamide adenine dinucleotide phosphate |
PAR | Protease-activated receptor |
ROS | Reactive oxygen species |
SIN-1 | Sydnonimine hydrochloride |
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Narita, Y.; Hamamura, K.; Kashiyama, M.; Utsumi, S.; Kakizoe, Y.; Kondo, Y.; Ishitsuka, Y.; Jono, H.; Irie, T.; Mukoyama, M.; et al. Edoxaban Exerts Antioxidant Effects Through FXa Inhibition and Direct Radical-Scavenging Activity. Int. J. Mol. Sci. 2019, 20, 4140. https://doi.org/10.3390/ijms20174140
Narita Y, Hamamura K, Kashiyama M, Utsumi S, Kakizoe Y, Kondo Y, Ishitsuka Y, Jono H, Irie T, Mukoyama M, et al. Edoxaban Exerts Antioxidant Effects Through FXa Inhibition and Direct Radical-Scavenging Activity. International Journal of Molecular Sciences. 2019; 20(17):4140. https://doi.org/10.3390/ijms20174140
Chicago/Turabian StyleNarita, Yuki, Kana Hamamura, Mami Kashiyama, Sara Utsumi, Yutaka Kakizoe, Yuki Kondo, Yoichi Ishitsuka, Hirofumi Jono, Tetsumi Irie, Masashi Mukoyama, and et al. 2019. "Edoxaban Exerts Antioxidant Effects Through FXa Inhibition and Direct Radical-Scavenging Activity" International Journal of Molecular Sciences 20, no. 17: 4140. https://doi.org/10.3390/ijms20174140