Reviewer's report
Title:Role of inducible nitric oxide synthase pathway on methotrexate-induced
intestinal mucositis in rodents
Version: 1Date:23 May 2011
Reviewer: Cuong Tran
Reviewer's report:
The aim of the present study was to investigate the role of nitric oxide (NO)
through the inducible nitric oxide synthase (iNOS) on the pathogenesis of
methotrexate-induced intestinal mucositis. The authors found that the
administration of MTX induced expression of iNOS. MTX-treated rats
administered with NOS inhibitors in particular aminoguanidine (AG) and L-NAME
significantly reduced villus and crypt damage, inflammatory response, apoptosis,
MPO activity and nitrotyrosine immunostaining. Furthermore, administration of
MTX in iNOS knockout mice did not caused significant inflammation. These data
suggests that iNOS may play an important role in the pathogenesis of intestinal
mucositis.
Overall the authors demonstrated some very interesting results. However, the
manuscript lacks clarity, succinctness and conciseness. There are lots of typo
and grammatical errors (writing style can be improved) which needs fixing
through more thorough proofreading. Sentences can be shorten and made
clearer.
Introduction
1. The introduction is too wordy and needs to be rewritten to make it more
concise.
Methods
1. Similarly, the materials and methods are too wordy for each section and can
be rewritten to make it more scientific.
2. The induction of mucositis in iNOS-/- and iNOS+/+ mice was not mentioned in
the materials and methods section. Are the doses and frequency the same as the
rats? Keep in mind that mice are more resistance to MTX and requires higher
doses to induce mucositis. The doses used in the rats would probably not induce
a significant intestinal mucositis in the mouse. This must be described in detail.
Results
1. Did the authors measure villus height/histology, cell proliferation, apoptosis
and immunohistochemistry in iNOS-/- and iNOS+/+ after the administration of
MTX? This will give an indication of the extent of the intestinal mucositis induced
by MTX of the same dose used in the rat. These data will be helpful in dissecting
the potential mechanism of iNOS in the MTX-induced mucositis.
2. These data reported by the authors suggests that iNOS may play an important
role in the pathogenesis of MTX-induced intestinal mucositis. However, it this
also consistent with other chemotherapy drugs such as 5-FU.
Discussion
1. The discussion is detailed but lack the in depth discussion it is a repetition of
what was mentioned in the results section.
Others
1. Figure legends too long need to shorten it.
2. Figure legend 3 “* p<0.05 represents statistical differences compared to MTX
group treated with saline (-)” this is right when referring to the graph.
3. Figure legend 4 “* p<0.05 represents statistical differences compared to
control group. ** p<0.05 represents statistical differences compared to MTX
group treated with saline (-)” there are no * and ** on figure 4. What do the
authors means by the above statements?
4. Table 1 should be described briefly in the text (materials and methods
section).
5. Table 3 will be better shown as a graph.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
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.
Reviewer's report
Title:Role of inducible nitric oxide synthase pathway on methotrexate-induced
intestinal mucositis in rodents
Version: 1Date:23 May 2011
Reviewer: Cuong Tran
Reviewer's report:
The aim of the present study was to investigate the role of nitric oxide (NO)
through the inducible nitric oxide synthase (iNOS) on the pathogenesis of
methotrexate-induced intestinal mucositis. The authors found that the
administration of MTX induced expression of iNOS. MTX-treated rats
administered with NOS inhibitors in particular aminoguanidine (AG) and L-NAME
significantly reduced villus and crypt damage, inflammatory response, apoptosis,
MPO activity and nitrotyrosine immunostaining. Furthermore, administration of
MTX in iNOS knockout mice did not caused significant inflammation. These data
suggests that iNOS may play an important role in the pathogenesis of intestinal
mucositis.
Overall the authors demonstrated some very interesting results. However, the
manuscript lacks clarity, succinctness and conciseness. There are lots of typo
and grammatical errors (writing style can be improved) which needs fixing
through more thorough proofreading. Sentences can be shorten and made
clearer.
Introduction
1. The introduction is too wordy and needs to be rewritten to make it more
concise.
Methods
1. Similarly, the materials and methods are too wordy for each section and can
be rewritten to make it more scientific.
2. The induction of mucositis in iNOS-/- and iNOS+/+ mice was not mentioned in
the materials and methods section. Are the doses and frequency the same as the
rats? Keep in mind that mice are more resistance to MTX and requires higher
doses to induce mucositis. The doses used in the rats would probably not induce
a significant intestinal mucositis in the mouse. This must be described in detail.
Results
1. Did the authors measure villus height/histology, cell proliferation, apoptosis
and immunohistochemistry in iNOS-/- and iNOS+/+ after the administration of
MTX? This will give an indication of the extent of the intestinal mucositis induced
by MTX of the same dose used in the rat. These data will be helpful in dissecting
the potential mechanism of iNOS in the MTX-induced mucositis.
2. These data reported by the authors suggests that iNOS may play an important
role in the pathogenesis of MTX-induced intestinal mucositis. However, it this
also consistent with other chemotherapy drugs such as 5-FU.
Discussion
1. The discussion is detailed but lack the in depth discussion it is a repetition of
what was mentioned in the results section.
Others
1. Figure legends too long need to shorten it.
2. Figure legend 3 “* p<0.05 represents statistical differences compared to MTX
group treated with saline (-)” this is right when referring to the graph.
3. Figure legend 4 “* p<0.05 represents statistical differences compared to
control group. ** p<0.05 represents statistical differences compared to MTX
group treated with saline (-)” there are no * and ** on figure 4. What do the
authors means by the above statements?
4. Table 1 should be described briefly in the text (materials and methods
section).
5. Table 3 will be better shown as a graph.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
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.
Please review this paper.
user
Reviewer's report
Title:Role of inducible nitric oxide synthase pathway on methotrexate-induced
intestinal mucositis in rodents
Version: 1Date:23 May 2011
Reviewer: Cuong Tran
Reviewer's report:
The aim of the present study was to investigate the role of nitric oxide (NO)
through the inducible nitric oxide synthase (iNOS) on the pathogenesis of
methotrexate-induced intestinal mucositis. The authors found that the
administration of MTX induced expression of iNOS. MTX-treated rats
administered with NOS inhibitors in particular aminoguanidine (AG) and L-NAME
significantly reduced villus and crypt damage, inflammatory response, apoptosis,
MPO activity and nitrotyrosine immunostaining. Furthermore, administration of
MTX in iNOS knockout mice did not caused significant inflammation. These data
suggests that iNOS may play an important role in the pathogenesis of intestinal
mucositis.
Overall the authors demonstrated some very interesting results. However, the
manuscript lacks clarity, succinctness and conciseness. There are lots of typo
and grammatical errors (writing style can be improved) which needs fixing
through more thorough proofreading. Sentences can be shorten and made
clearer.
Introduction
1. The introduction is too wordy and needs to be rewritten to make it more
concise.
Methods
1. Similarly, the materials and methods are too wordy for each section and can
be rewritten to make it more scientific.
2. The induction of mucositis in iNOS-/- and iNOS+/+ mice was not mentioned in
the materials and methods section. Are the doses and frequency the same as the
rats? Keep in mind that mice are more resistance to MTX and requires higher
doses to induce mucositis. The doses used in the rats would probably not induce
a significant intestinal mucositis in the mouse. This must be described in detail.
Results
1. Did the authors measure villus height/histology, cell proliferation, apoptosis
and immunohistochemistry in iNOS-/- and iNOS+/+ after the administration of
MTX? This will give an indication of the extent of the intestinal mucositis induced
by MTX of the same dose used in the rat. These data will be helpful in dissecting
the potential mechanism of iNOS in the MTX-induced mucositis.
2. These data reported by the authors suggests that iNOS may play an important
role in the pathogenesis of MTX-induced intestinal mucositis. However, it this
also consistent with other chemotherapy drugs such as 5-FU.
Discussion
1. The discussion is detailed but lack the in depth discussion it is a repetition of
what was mentioned in the results section.
Others
1. Figure legends too long need to shorten it.
2. Figure legend 3 “* p<0.05 represents statistical differences compared to MTX
group treated with saline (-)” this is right when referring to the graph.
3. Figure legend 4 “* p<0.05 represents statistical differences compared to
control group. ** p<0.05 represents statistical differences compared to MTX
group treated with saline (-)” there are no * and ** on figure 4. What do the
authors means by the above statements?
4. Table 1 should be described briefly in the text (materials and methods
section).
5. Table 3 will be better shown as a graph.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
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.
assistant