Review for 10.1186/1471-230X-12-35 (2012)

Reviewer's report
Title:Apolipoprotein E COG 133 mimetic peptide improves
5-fluorouracil-induced intestinal mucositis
Version: 2Date:9 August 2011
Reviewer: Jerzy-Roch Nofer
Reviewer's report:
In the manuscript entitled „Apolipoprotein E COG 133 mimetic peptide improves
5-fluorouracil-induced intestinal mucositis” Azevedo and colleagues describe
beneficial effects of apoE mimetic on epithelial damage in 5FU-treated mice.
While this seems to be the first report showing that apolipoprotein mimetics
protect against chemotherapy-induced intestine cytotoxicity, salutary effects of
apoE COG 133 were previously shown in a mice model of colitis. The study
encompasses both in vivo and in vitro approaches and is generally
well-performed. However, the rationale for the study is unclear, the study is
rather descriptive with little mechanical insights, and the manuscript requires
thorough editing. The specific comments (major compulsary revision) are as
follows:
1. The rationale for the study is unclear. Why did the authors use apoE mimetics
and not other apolipoprotein mimetics or - more generally - other
anti-inflammatory compounds? Protective effects of apoE mimetics seen in
traumatic brain injury (as pointed by the authors in the Introduction) certainly do
not provide sufficient explanation.
2. The major drawback of the study is that it does not provide any insight into
mechanisms underlying protective effects of apoE COG 133. In particular, it is
not clear whether these effects are apoE-specific and/or apoE-receptor-specific
or can be attributed to the amphipatic properties of apoE mimetic, which are
shared with other apolipoprotein mimetics such as apoA-I mimetics. To address
this question the authors should:
- provide more information about the structure of apoE COG 133 and its
amphipaticity and hydrophobic moment
- assess the 5FU-induced epithelial damage in apoE deficient mice (which are
commercially available) and whether this damage can be reversed by apoE COG
133
- compare the effect of apoE COG 133 on the 5FU-induced epithelial damage in
vivo with standard apoA-I mimetic (i.e. D4-F)
- assess anti-apoptotic and migration-stimulating effects of apoE COG 133 in
vitro in the presence of RAP, which inhibits apoE binding to receptors, as well as
compare the effects of apoE COG 133 with the effects of apoA-I mimetic
3. The assessment of effects of apoE COG 133 on the inflammatory response is
not sufficient. The study should also include:
- immunochemical characterization of inflammation in the intestine with particular
focus on macrophages and lymphocytes, and – if possible (discretionary) –
functional polarization of these cells (M1 vs. M2; Th1 vs. Th2)
- determination of inflammation and polarization markers in blood
- assessment of the activation of NF-kB pathway in the intestine (discretionary)
- determination of IL-1ra levels in the intestine tissue and blood. The latter
parameter seems to exert a key role in the intestinal inflammatory response
following 5FU treatment
4. The discussion at present resembles a rather random collection of loose
commentaries on previously published papers. It has to be re-written to focus
more on the results of the present study.
5. The manuscript seems to be put together rather hastily and is quite sloppily
edited with several inconsistencies in abbreviations and reference format, typos,
etc. The authors should definitely pay more attention to details!!!
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests