Review for 10.1186/s12876-020-01532-4 (2021)

Reviewer’s report
Title: 
Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal
absorption of octreotide in rats with portal hypertension
Version: 
0 
Date: 
10 Apr 2019
Reviewer: 
Marcus Hollenbach
Reviewer's report:
Comment to the editor
This study by Tang et al analyzed the effect of octreotide on portal hypertension.
They concluded that octreotide (OCT) absorption is impaired in a model of
portal hypertension (bile duct ligation). Also, resorption is dependent on P-gp
and MRP2. Although this is an interesting study, several findings need to be
addressed before considering this manuscript for publication in "BMC
Gastroenterolology". 
Major concerns
First, this topic is not new. It is known for several years that OCT reduces portal
hypertension and is an alternative to terlipressin. Nevertheless, OCT is mostly
intravenous given in clinical setting. Also, since LAR with long acting
mechanism are available. So, what is the clinical relevance of this work. Please
justify.
The experiments are performed in a bile duct ligation model of portal
hypertension. Since this model reflects more a presinusoidal intrahepatic portal
hypertension, this is also a rare clinical condition (e.g. PBC). In most cases,
portal hypertension is caused intrahepatic instrasinusoidal, mostly by alcohol or
hepatitis. The CCl4-induced cirrhosis in Wistar rats is a reliable model and more
related to clinical condition. Why the authors did not us this model. Please
justify. Is it possible to perform the experiments in this setting?
What is the rationale for measuring CYP3A, MRP2 and P-gp? What could be the
mechanism behind? These data are very preliminary although discussed by the
authors.
Portal pressure was not measured. How the authors proved that the rats
developed portal hypertension?
Housekeeping genes of Beta-Actin and others are known to be regulated in
cirrhosis. Why the authors did not use PPIB instead? Please justify.
The authors analyzed in statistics often more than two groups but used Mann-
Whitney test (only for two groups evaluated). Why ANOVA was not used?
Please justify.
Why use supplemental material when only 5 figures are presented?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
'I declare that I have no competing interests'
I agree to the open peer review policy of the journal. I understand that my name
will be included on my report to the authors and, if the manuscript is accepted
for publication, my named report including any attachments I upload will be
posted on the website along with the authors' responses. I agree for my report to
be made available under an Open Access Creative Commons CC-BY license
(
http://creativecommons.org/licenses/by/4.0/
). I understand that any comments
which I do not wish to be included in my named report can be included as
confidential comments to the editors, which will not be published.
I agree to the open peer review policy of the journal