# СȱѪٹע

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Dear Mr. Zheng:
 I am pleased to inform you that your manuscript entitled "Hydrogen-Rich Saline Protects against Intestinal Ischemia/Reperfusion Injury in Rats" has been accepted for publication in Free Radical Research.  The comments of the reviewer(s) who reviewed your manuscript are included below.
Thank you for your fine contribution.  On behalf of the Editors of Free Radical Research, we look forward to your continued contributions to the Journal.
 Sincerely,
Prof. Michael Davies
Editor, Free Radical Research
daviesm@hri.org.au
 Reviewer(s)' Comments to Author:
Reviewer: 1
Comments to the Author
The authors have carried out the required additional experiments and analyses.

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Hydrogen-Rich Saline Protects against Intestinal Ischemia/Reperfusion Injury in Rats

Abstract

Hydrogen gas was reported to reduce reactive oxygen species and alleviate cerebral, myocardial and hepatic ischemia/reperfusion (I/R) injuries.  We studied the effect of hydrogen-rich saline, which was easier for clinical application, on the intestinal I/R injury.  In male Sprague–Dawley rats, intestinal injury was induced by clamping the superior mesenteric artery for 45 minutes, followed by 120 min reperfusion.  Hydrogen-rich saline or vehicle physiological saline (5 ml/kg) was administered via intravenous infusion 10 minutes before reperfusion, respectively.  The intestine damage was detected microscopically and was assessed by Chiu score system after I/R injury. In addition, serum DAO activity, tissue MDA and MPO activity, serum TNF-α, IL-1β and IL-6 levels were all increased significantly by I/R injury. Hydrogen-rich saline reduced these tissue injury markers and relieved morphological intestinal injury. In conclusion, Hydrogen-rich saline protected the small intestine against I/R injury possibly by reduction of inflammation and oxidative stress.

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Dear Dr. Zheng:

The manuscript ID GFRR-2008-0266 entitled "Hydrogen-Rich Water Protects against Intestinal Ischemia/Reperfusion Injury in Rats", which you submitted to Free Radical Research, has been reviewed by two external experts.  The comments from these two reviewers are included below.

In view of the criticisms of the reviewers, I must decline the manuscript for publication in Free Radical Research at this time.  Therefore, please feel free to submit your work to another journal.

However, we would be prepared to consider a NEW manuscript on this subject area which takes into consideration the comments made by the reviewers.

The submission of such a manuscript does not guarantee eventual acceptance, and any resubmission would be subject to re-review by the reviewers before a decision is rendered. As you will see both of the reviewers feel that considerable extra experimental work and details would be required to make the current work suitable for publication.

You will not be able to make alterations to the originally submitted version of your manuscript.  Instead, write your manuscript using a word processing program and save it on your computer. Please indicate the changes made to the old version item by item in a separate letter.

Once you have revised your manuscript, go to http://mc.manuscriptcentral.com/gfrr
  and login to your Author Center.  Click on "Manuscripts with Decisions," and then click on "Create a Resubmission" located next to the manuscript number.  Then, follow the steps for resubmitting your manuscript.


Reviewer: 1
The authors studied the effect of intravenous injection of hydrogen saline to ischemia/reperfusion injury of intestine.  This is the first report showing the effect of intravenous injection of hydrogen saline.  I think that this manuscript contains a very exciting result.  This method has very high potential to be applied to an actual clinical use.  However, I have some significant concerns.

(1) The authors did not describe details of how to inject hydrogen saline.  Where did the authors inject hydrogen saline?  How many minutes did the authors take to inject hydrogen saline? and so on.  The authors should describe the details as much as possible.
(2) The authors used the term "H2 water or physiological saline".  The description may lead to unnecessary confusions.  In previous reports, hydrogen water was used to let animals drink it.  Since the authors did not use water but only saline, hydrogen saline should be right.  Throughout the manuscript, the unnecessary confusion should be avoided.
(3) Did the authors measure the blood concentration of hydrogen after intravenous injection of hydrogen saline?  It is very important to show the concentration of hydrogen.
At least, the authors should discuss the issues by citing previous reports.

(4) In Figure 1, panel D is too small.  None can read the letters in panel D.
(5) In references, the authors should cite a paper of Buchholz et al. Hydrogen Inhalation Ameliorates Oxidative Stress in Transplantation Induced Intestinal Graft Injury. Am J Transplant. 2008 Aug; 8:2015-24.

Reviewer: 2
The authors have cited a Nature medicine paper (ref#7) which was a very interesting study looking at hydrogen gas, not solutions of hydrogen gas which has been used in this current study yet the manuscript is written to imply the two studies are comparable. The study is largely observational and offers little mechanistic insight.  The description of the methods is very poor and the majority of the work (on H2 gas) from what I can tell has been done elsewhere. The results are essentially one figure.

The authors do not state how they made their
hydrogen water?
or how they keep the hydrogen in solution. If their H2-saturated water is open to the air, the H2 saturated solution will just start equilibrating with the air as soon as they stop bubbling H2 through the water. Therefore, neither the concentration of H2 added  nor the effective concentrations of H2 can be determined.

Additionally, what is the solubility of H2? The authors dose of H2-saturated (presumably, this has not been determined) water of 5ml/kg corresponds to about 1ml per rat. The total blood volume of an adult rat is in the region of 8ml. So what is the final concentration of H2? What are the effects of adding this volume (of water) alone on cardiovascular function? What controls were performed? Bubbling the solutions with H2 will remove O2 present in the water, so a corresponding de-oxygenated sample would be required as a control (e.g. a solution subject to N2 gassing).

The authors state that H2 might work as an antioxidant because it reacts with hydroxyl radicals. However, so does everything. At least further mechanisms should be determined.

200901

2010.01

http://blog.sciencenet.cn/blog-41174-214181.html

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