Reviewer's report
Title:Protective effects of N-acetylcysteine on acetic acid-induced colitis in a
porcine model
Version: 1Date:16 May 2013
Reviewer: Francois FB Blachier
Reviewer's report:
The manuscript by Wang et al. contains potentially important and timely new
informations regarding dietary supplementation with N-acetylcysteine in a context
of large intestine inflammation. In addition, the experiments appear to have been
carefully done. However, in my opinion, some changes have to be made in the
paper in order to better explain some aspect of the experimental work performed,
to fully interpret some results obtained and to moderate some conclusions made.
1. The experimental protocol for colitis induction and dietary supplementation in
not clearly explained, and a schematic figure is necessary to better explain the
experimental design with indication of the time when piglets received the injection
of acetic acid in the lumen of their large intestine, and time at which the dietary
supplementation with N-acetylcysteine was done.
2. According to the biochemical parameters measured after colitis induction in
piglets, it appears that the experimental colitis was relatively "light". Indeed, by
looking for instance at the MPO activity and measurement of the proinflammatory
cytokine TNF-alpha, it appears that, compared with other model of
chemically-induced colitis (DSS etc. see the bibliographic data available), the
experimental colitis was mild. This should be clearly said in order to fully interpret
the results obtained. In addition, apparently, there was no major anorexic effect
of acetic acid treatment, in contrast with model of more severe colitis induction in
which the anorexic effect is drastic.
3. The measurement of claudin-1 protein by Western blot is relatively distal
regarding the tight junction function, since this function depends on numerous
proteins as well as their molecular organization between cells. Thus, no firm
conclusion can be made from only measurement of claudin expression; and this
needs to be discussed.
4. In medical practice, the treatment of colitis is generally done through
pharmacological intervention (anti-TNF alpha, corticosteroids etc.), and thus
dietary supplementation should be regarded as possible adjuvant therapy, even if
extrapolation from the acetic acid-treated piglet to human disease (Crohn's and
ulcerative colitis) is somewhat hazardous. Anyway, the model presented,
considering that piglet intestinal physiology and physiopathology are likely less
vastly different than intestinal physiology in rodents, is interesting, and needs to
be discussed more.
5. Can N-acetylcysteine be clived into cysteine in intestinal epithelial cells or
elsewhere in the body? If so, one can speculate that it will increase cysteine
bioavailability for glutathion synthesis in enterocytes and colonocytes. If so, this
may be a way by which NAC protect these cells from reactive oxygen species
deleterious effect. This is not discussed in the initial version of the paper.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interest
Reviewer's report
Title:Protective effects of N-acetylcysteine on acetic acid-induced colitis in a
porcine model
Version: 1Date:16 May 2013
Reviewer: Francois FB Blachier
Reviewer's report:
The manuscript by Wang et al. contains potentially important and timely new
informations regarding dietary supplementation with N-acetylcysteine in a context
of large intestine inflammation. In addition, the experiments appear to have been
carefully done. However, in my opinion, some changes have to be made in the
paper in order to better explain some aspect of the experimental work performed,
to fully interpret some results obtained and to moderate some conclusions made.
1. The experimental protocol for colitis induction and dietary supplementation in
not clearly explained, and a schematic figure is necessary to better explain the
experimental design with indication of the time when piglets received the injection
of acetic acid in the lumen of their large intestine, and time at which the dietary
supplementation with N-acetylcysteine was done.
2. According to the biochemical parameters measured after colitis induction in
piglets, it appears that the experimental colitis was relatively "light". Indeed, by
looking for instance at the MPO activity and measurement of the proinflammatory
cytokine TNF-alpha, it appears that, compared with other model of
chemically-induced colitis (DSS etc. see the bibliographic data available), the
experimental colitis was mild. This should be clearly said in order to fully interpret
the results obtained. In addition, apparently, there was no major anorexic effect
of acetic acid treatment, in contrast with model of more severe colitis induction in
which the anorexic effect is drastic.
3. The measurement of claudin-1 protein by Western blot is relatively distal
regarding the tight junction function, since this function depends on numerous
proteins as well as their molecular organization between cells. Thus, no firm
conclusion can be made from only measurement of claudin expression; and this
needs to be discussed.
4. In medical practice, the treatment of colitis is generally done through
pharmacological intervention (anti-TNF alpha, corticosteroids etc.), and thus
dietary supplementation should be regarded as possible adjuvant therapy, even if
extrapolation from the acetic acid-treated piglet to human disease (Crohn's and
ulcerative colitis) is somewhat hazardous. Anyway, the model presented,
considering that piglet intestinal physiology and physiopathology are likely less
vastly different than intestinal physiology in rodents, is interesting, and needs to
be discussed more.
5. Can N-acetylcysteine be clived into cysteine in intestinal epithelial cells or
elsewhere in the body? If so, one can speculate that it will increase cysteine
bioavailability for glutathion synthesis in enterocytes and colonocytes. If so, this
may be a way by which NAC protect these cells from reactive oxygen species
deleterious effect. This is not discussed in the initial version of the paper.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interest
Please review this paper.
user
Reviewer's report
Title:Protective effects of N-acetylcysteine on acetic acid-induced colitis in a
porcine model
Version: 1Date:16 May 2013
Reviewer: Francois FB Blachier
Reviewer's report:
The manuscript by Wang et al. contains potentially important and timely new
informations regarding dietary supplementation with N-acetylcysteine in a context
of large intestine inflammation. In addition, the experiments appear to have been
carefully done. However, in my opinion, some changes have to be made in the
paper in order to better explain some aspect of the experimental work performed,
to fully interpret some results obtained and to moderate some conclusions made.
1. The experimental protocol for colitis induction and dietary supplementation in
not clearly explained, and a schematic figure is necessary to better explain the
experimental design with indication of the time when piglets received the injection
of acetic acid in the lumen of their large intestine, and time at which the dietary
supplementation with N-acetylcysteine was done.
2. According to the biochemical parameters measured after colitis induction in
piglets, it appears that the experimental colitis was relatively "light". Indeed, by
looking for instance at the MPO activity and measurement of the proinflammatory
cytokine TNF-alpha, it appears that, compared with other model of
chemically-induced colitis (DSS etc. see the bibliographic data available), the
experimental colitis was mild. This should be clearly said in order to fully interpret
the results obtained. In addition, apparently, there was no major anorexic effect
of acetic acid treatment, in contrast with model of more severe colitis induction in
which the anorexic effect is drastic.
3. The measurement of claudin-1 protein by Western blot is relatively distal
regarding the tight junction function, since this function depends on numerous
proteins as well as their molecular organization between cells. Thus, no firm
conclusion can be made from only measurement of claudin expression; and this
needs to be discussed.
4. In medical practice, the treatment of colitis is generally done through
pharmacological intervention (anti-TNF alpha, corticosteroids etc.), and thus
dietary supplementation should be regarded as possible adjuvant therapy, even if
extrapolation from the acetic acid-treated piglet to human disease (Crohn's and
ulcerative colitis) is somewhat hazardous. Anyway, the model presented,
considering that piglet intestinal physiology and physiopathology are likely less
vastly different than intestinal physiology in rodents, is interesting, and needs to
be discussed more.
5. Can N-acetylcysteine be clived into cysteine in intestinal epithelial cells or
elsewhere in the body? If so, one can speculate that it will increase cysteine
bioavailability for glutathion synthesis in enterocytes and colonocytes. If so, this
may be a way by which NAC protect these cells from reactive oxygen species
deleterious effect. This is not discussed in the initial version of the paper.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interest
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