Edoxaban Exerts Antioxidant Effects Through FXa Inhibition and Direct Radical-Scavenging Activity
| Autor: | Mami Kashiyama, Yuki Narita, Sara Utsumi, Yuki Kondo, Kenichiro Kitamura, Hirofumi Jono, Yoichi Ishitsuka, Sumio Hirata, Tetsumi Irie, Yutaka Kakizoe, Kana Hamamura, Daisuke Kadowaki, Hideyuki Saito, Masashi Mukoyama |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Antioxidant factor Xa Pyridines medicine.medical_treatment antioxidant effect 030204 cardiovascular system & hematology Pharmacology medicine.disease_cause lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine Edoxaban lcsh:QH301-705.5 Spectroscopy Protease-activated receptor 2 chemistry.chemical_classification reactive oxygen species General Medicine Free Radical Scavengers Computer Science Applications medicine.symptom medicine.drug Inflammation Catalysis Article Cell Line Inorganic Chemistry 03 medical and health sciences medicine Humans Physical and Theoretical Chemistry Molecular Biology Rivaroxaban Reactive oxygen species Hydroxyl Radical Organic Chemistry Electron Spin Resonance Spectroscopy Anticoagulants Angiotensin II Oxidative Stress Thiazoles 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 chemistry edoxaban protease-activated receptor 2 Oxidative stress Factor Xa Inhibitors |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 20, Iss 17, p 4140 (2019) Volume 20 Issue 17 |
| ISSN: | 1422-0067 |
| Popis: | The interplay between oxidative stress, inflammation, and tissue fibrosis leads to the progression of chronic kidney disease (CKD). Edoxaban, an activated blood coagulation factor Xa (FXa) inhibitor, ameliorates kidney disease by suppressing inflammation and tissue fibrosis in animal models. Interestingly, rivaroxaban, another FXa inhibitor, suppresses oxidative stress induced by FXa. Thus, FXa inhibitors could be multitargeted drugs for the three aforementioned risk factors for the progression of CKD. However, the exact mechanism responsible for eliciting the antioxidant effect of FXa inhibitors remains unclear. In this study, the antioxidant effect of edoxaban was evaluated. First, the intracellular antioxidant properties of edoxaban were evaluated using human proximal tubular cells (HK-2 cells). Next, direct radical scavenging activity was measured using the electron spin resonance and fluorescence analysis methods. Results show that edoxaban exhibited antioxidant effects on oxidative stress induced by FXa, indoxyl sulfate, and angiotensin II in HK-2 cells, as well as the FXa inhibitory activity, was involved in part of the antioxidant mechanism. Moreover, edoxaban exerted its antioxidative effect through its structure-specific direct radical scavenging activity. Edoxaban exerts antioxidant effects by inhibiting FXa and through direct radical-scavenging activity, and thus, may serve as multitargeted drugs for the three primary risk factors associated with progression of CKD. |
| Databáze: | OpenAIRE |
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