Review for 10.1186/1471-230X-5-37 (2005)

Reviewer's report 
 Protective effect of leptin against ischemia-reperfusion injury in the rat small intestine Title: 
 2  20 July 2005 Version: Date: 
 Thomas Brzozowski Reviewer: 
Reviewer's report: 
General 
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X Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
X - MAJOR REVISON 
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Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
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Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article of limited interest Level of interest: 
 Needs some language corrections before being published Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
In this paper, the protective activity of leptin, a hormone involved in the control of appetite, was 
investigated in the rat model of intestinal ischemia-reperfusion (I/R). Five group of rats received 
placebo or leptin without or with the combination with L-NAME and they were subjected to occlusion 
of mesenteric artery for 45 min to induce ischemia and followed by release of clamp to perform 
reperfusion for 120 min. Following reperfusion, the small intestines were resected for the determination of malonyloaldehyde (MDA) and nitric oxide (NO) levels and for the assessment of 
intestinal mucosal injury by histological score. I/R caused the mucosal injury and increased the MDA 
concentration while decreasing intestinal tissue level of NO and these effects were reversed by leptin. The intestinal damage induced by I/R was also significantly reduced by leptin and this effect 
was not affected by co-treatment of leptin with L-NAME. It is concluded that leptin can attenuate the 
intestinal injury via increase in the vasodilatation of mesenteric vessels and implies it usefulness in 
the intestinal surgery. 
Overall, this paper adds not many more to the previous already accumulated evidence indicating that 
NO may participate to the protective action of this hormone in the GI tract including stomach and 
intestine. Some issues require authors clarification and response to the reviewer comments and 
queries, before the final decision regarding this paper. 
Critical comments: 
1. The authors should definitely specify what is new in their paper as compared to the published 
evidence on leptin and NO in the intestine and this comment need to be inserted in the Introduction. 
2. Why leptin was administered after ischemia but not prior to the onset of ischemia? A comment on 
that is necessary in the Material and Methods. 
3. The conclusion that leptin induces vasodilatation of the mesentery beds (abstract conclusion, 
page 1 and Discussion, page 9) is not supported by the evidence because neither functional determination of intestinal blood flow nor intestinal capillary diameter were determined. 4. Does leptin have a direct vasodilatory effect on blood vessels or rather NO released by leptin 
exerts possible vasodilatory effect (page 9)? This need to be answered and the comment on that 
should included. 
5. What was the reason to determine the NO content in the intestinal tissue instead of measurement 
of NO in the intestinal lumen? NO released in the intestinal lumen may be responsible for the 
protective activity of leptin. 
6. The explanation is needed why the treatment with leptin failed to significantly affect the decrease in NO and lesion score in rats treated with L-NAME? 7. The conclusion of the study would be strengthen by results with the additional group receiving 
L-arginine, a substrate for NO-synthase, added to leptin in animals treated with L-NAME. 
Minor: 1. The picture of the ischemic intestine vs that protected by leptin can enrich the paper. 2. Please uniform throughout the text: mesenteric artery or arteria mesenteric superior. 
3. For sake of clarity is better to disclose five groups (I-V) in Results and Tables and define them as 
placebo + Leptin, L-NAME + Leptin, Leptin alone etc., because this can be immediately identified by 
the Reader. Significance labeling should be different for the group comparisons (asterisk, crosses) 
and explained in the description of Tables.