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Volume 20
Issue 17
10.3390/ijms20174140
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Article
Peer-Review Record

Edoxaban Exerts Antioxidant Effects Through FXa Inhibition and Direct Radical-Scavenging Activity

Int. J. Mol. Sci. 2019, 20(17), 4140; https://doi.org/10.3390/ijms20174140
by Yuki Narita 1,2,*, Kana Hamamura 3, Mami Kashiyama 3, Sara Utsumi 3, Yutaka Kakizoe 4, Yuki Kondo 5, Yoichi Ishitsuka 5, Hirofumi Jono 1,2, Tetsumi Irie 5, Masashi Mukoyama 4, Hideyuki Saito 1,2, Daisuke Kadowaki 6, Sumio Hirata 3 and Kenichiro Kitamura 7
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Int. J. Mol. Sci. 2019, 20(17), 4140; https://doi.org/10.3390/ijms20174140
Submission received: 9 August 2019 / Revised: 21 August 2019 / Accepted: 21 August 2019 / Published: 24 August 2019
(This article belongs to the Special Issue Molecular Mechanisms and Biomarkers in Drug-Induced Organ Injury)

Round 1

Reviewer 1 Report

Authors have elucidated the role of edoxaban as a potential treatment for chronic kidney disease by eliciting antioxidant properties through inhibition of FXa and direct radical scavenging activity. Experimental design is good and technically manuscript is sound. Authors did a thorough job in measuring the ROS production through spectroscopy. However authors should provide more data to prove their point. I have some minor concerns which are as follows:

Please design some experiments regarding morphology of the cells with respect to ROS production. For superoxide and H2O2  show differential staining. For maintaining existing the tittle of the paper authors should provide more mechanistic  details. More specifically some new experiments related to in vivo diabetic mice model, then only we can say that edoxaban is a potential molecule for treating CKD. 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

This in-vitro model on tubular cells demonstrates elegantly the capacity of Edobaxan to strongly mitigate oxydative stress at cellular level via both factor Xa  pathway and other pleiotropic effects and its potential ability to lessen inflammation observed in CKD.

Authors should in their discussion add a paragraph on the adaptation of the dosage of the molecule in CKD patients not on dialysis (with a first step at moderate CKD and a second step when severe CKD is reached) together with its contraindication in those patients on dialysis (Jain N and Reilly F; Clinical pharmacology of oral anticoagulants in patients with kidney disease . CJASN 2019; 14: 278-287 )

Author Response

Please see the attachment.

Author Response File: Author Response.docx

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