Roles of Reactive Oxygen Species and Autophagy in the Pathogenesis of Cisplatin-Induced Acute Kidney Injury

Round 1

Reviewer 1 Report

In the review article, "Roles of reactive oxygen species and autophagy in the pathogenesis of cisplatin-induced AKI," the authors provide a nice, succinct overview of the topic.

The only comment regard the pictures that are difficut to understand and do not add anything to the text.

Author Response

Thanks for the good evaluation to our manuscript. According to the suggestion, we tried to change the figures for understandable pictures. But, it was too difficult for us to amend the pictures this time. For more clarification, we know a couple of pictures need anymore. We would like to provide them at the future opportunity.

Reviewer 2 Report

The paper "Roles of reactive oxygen species ans auttophagy in the pathogeneis of cisplatin-induced acute kidney injury" by Yoshikawa S, et al. is interesting  and propose a new approach to limited the progression of kidney injury caused by cisplatin. They proposed the utilisation of some microorganisms of gut microbiota in order to improve the efficacy and reduce the toxicity of the chemotherapeutic agents. Slow progression  of AKI and CDK through increasing SCFAs production may be ascribed to the utilisation of probiotics, such as L. reuterii and C. butyricum. 

This type of therapy is interesting and well known, but now we are in the era of antibiotics resistance. The utilisation of microrganisms such as Lactobacillus reuterii and Clostridium butyricum that are probiotic and therefore resistant to the majority of antibiotics can be a gamble. They can transmit resistance characters to other microrganisms and caused important infections and we would no longer have useful antibiotics... Probably from now on they will have to be used carefully given this characteristic!

Author Response

Thanks for the critical evaluation to our manuscript. According to the suggestion, we have added the explanation related to this matter at the end of “5. Future perspectives” as well as the extra reference-86.

Reviewer 3 Report

Comments in General:

The authors give an overview oft he literature of factors influencing renal nephrotoxicity of cisplatin-induced acute kidney injury.

They are concentrating herein on newer literature about reactive oxygen species (ROS) and autophagy. Eightyfive citations oft he literature are given, of which 44% have have been published between 2020 and 2022 (13% even 2022!) and only 31% before 2016. Two figures illustrating cixplatin-induced acute kidney injury by ROS and counteraction by autophagy (Figure 1) as well as examples of mediators of autophagy and support of the gut-kidney axis by pro- and prebiotics as well as fecal microbiota transplantation (Figure 2) are also given. Established mechanisms of eliminating or anti-acting ROS as well as inducing autophagy are the central message oft he article with support oft he gut-kidney axis. Examples for therapeutic measures on ROS and autophagy including medical agents and natural compounds as well as supporting measures on the gut-kidney axis are given.

This is a useful overview of the main limiting side effect (nephrotoxicity) of an otherwise very effective old and trusted anti-cancer medicament (cisplatin) with the nowadays possibilities to interfere with nephrotoxicity.   

Special Comment:

In the Reference List, in No. 25 and 74 the name oft he Journal is missing.

Author Response

Thanks for the good evaluation to our manuscript. According to the suggestion, we have added the Journal names of reference-No. 25 and 74 in the Reference List.