Review for 10.1186/s12876-021-01640-9 (2021)

Reviewer’s report
Title: 
Pre-inhalation of hydrogen-rich gases protect against caerulein-induced
mouse acute pancreatitis while enhance the pancreatic Hsp60 protein expression
Version: 
1 
Date: 
12 Sep 2020
Reviewer's report:
This manuscript described protective roles of hydrogen-rich gas inhalation in the
mouse model of acute pancreatitis. This treatment attenuated the degree of
inflammation, inflammatory mediators and oxidative stress via the induction of
Hsp60. Presented data suggested possibility of this new treatment for acute
pancreatitis. However, several points are need to be clarified to make this
manuscript more informative. Followings are my comments. 
1. 
Effects of hydrogen rich gas inhalation need to be evaluated more in detail.
Concentration of hydrogen in blood or tissue samples should be presented. In
addition, safety of repeated hydrogen rich gas inhalation should be assessed for
clinical application. 
2. 
In this study, pretreatment attenuated inflammation caused by following
caerulein treatment. Authors should examine the effects of hydrogen rich gas
inhalation after caerulein injection. 
3. 
Efficacy of this new treatment should be compared with conventional
antioxidant therapy such as NAC or other agents. This experiment will reinforce
authors' claim. 
4. 
Protective effects of hydrogen gas should be assessed also in in vitro settings.
Use of AR42J cells or primary cultured acinar cells will be suitable. Changes in
intracellular signaling such as MAPK or apoptotic pathways are intriguing
targets. 
5. 
Use of other pancreatitis models will reinforce authors' working hypothesis.
Ethanol/palmitic acid model will be an adequate choice. 
6. 
Effects of hydrogen gas to pancreatic stellate cells are additional interests. Please
consider additional experiments. 
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Is the study design appropriate to answer the research question (including the use
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