Reviewer's report
Title:Nrf2-mediated heme oxygenase-1 induction of PPI confers adaptive
survival response to NSAID-induced gastric damages
Version: 1Date:30 June 2012
Reviewer: Kazuhide Higuchi
Reviewer's report:
The author reported that pantoprazole can protect stomach against
NSAIDs-induced damages by not only acid suppression but also Nrf2-driven
HO-1 induction which occurs the improvement of NSAIDs-induced ischemia,
attenuation of adhesion molecule, and decreasing inflammatory mediators. This
study is interest. In vitro angiogenesis assay, the author reported that
pantoprazole increase expression of angiogenic factors and activate
NSAIDs-induced angiogenesis. However, there are some problems.
Comments to the author
Major
(1) The author reported that pantoprazole improve NSAIDs-induced ischemia.
However, in this study, although pantoprazole increase expression of angiogenic
factors and activate NSAIDs-induced angiogenesis, it is not enough persuasive
to conclude that pantoprazole improve the ischemia. The authors should discuss
about this point.
(2) In Figure2A, the author demonstrated that Western blots for either cytosolic
keap1 or nuclear Nfr2 in a different time in the presence of 300 M pantoprazole.
However, the author did not describe whether the lower concentration of
pantoprazole could increase cytosolic keap1 and nuclear Nfr2 or not.
(3) Figure4 and Figure5 showed that indomethacin alone did not increase the
expression of HO-1. However, indomethacin induced inflammation. Some reports
found that indomethacin increased the expression of HO-1. The authors should
discuss about this point.
(4) Figure4 and Figure5 showed that ZnPP# decreased the expression of HO-1. I
think that ZnPP# inhibit only activity of HO-1. Can ZnPP# decrease the
expression of HO-1?
(5) Figure3C showed that pantoprazole increased the expression of HIF-1.
However, Figure5 showed that pantoprazole decreased HIF-1-#-DNA binding. It
seems contradictory.
(6) The authors think all PPIs may induce HO-1 from the discussion. However,
Yoda et al. (J Physiol Pharmacol. 2010 Jun;61(3):287-94) reported that
lansoprazole, but not omeprazole, induced HO-1. The authors should refer this
paper and discuss about this point.
Minor
(1) There is Figure2E which show the change of DCF-DA fluorescence after
different dosing of pantoprazole. However, in Figure legend, there is no
description of Figure2E. Is Figure2E the part of Figure2D?
(2) In p.8 l.23, the author described “PPI also increased expression of VEGF,
mRNA and protein levels(Figure2A) in RGM-1 gastric mucosal cells.” However,
not Figuer2A but Figure3A showed the expression of VEGF.
(3) In p.9 l.16-18, the author described “Additionally indomethacin challenge
significantly increased the expressions of NADPH oxidase-1(NOX-1) as seen in
Fig.4B”. However, Weston blotting of NOX-1 is shown in Figure4A.
(4) In p.10 l.16, the author described “ICAL-1”. Is it mistake?
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.
Reviewer's report
Title:Nrf2-mediated heme oxygenase-1 induction of PPI confers adaptive
survival response to NSAID-induced gastric damages
Version: 1Date:30 June 2012
Reviewer: Kazuhide Higuchi
Reviewer's report:
The author reported that pantoprazole can protect stomach against
NSAIDs-induced damages by not only acid suppression but also Nrf2-driven
HO-1 induction which occurs the improvement of NSAIDs-induced ischemia,
attenuation of adhesion molecule, and decreasing inflammatory mediators. This
study is interest. In vitro angiogenesis assay, the author reported that
pantoprazole increase expression of angiogenic factors and activate
NSAIDs-induced angiogenesis. However, there are some problems.
Comments to the author
Major
(1) The author reported that pantoprazole improve NSAIDs-induced ischemia.
However, in this study, although pantoprazole increase expression of angiogenic
factors and activate NSAIDs-induced angiogenesis, it is not enough persuasive
to conclude that pantoprazole improve the ischemia. The authors should discuss
about this point.
(2) In Figure2A, the author demonstrated that Western blots for either cytosolic
keap1 or nuclear Nfr2 in a different time in the presence of 300 M pantoprazole.
However, the author did not describe whether the lower concentration of
pantoprazole could increase cytosolic keap1 and nuclear Nfr2 or not.
(3) Figure4 and Figure5 showed that indomethacin alone did not increase the
expression of HO-1. However, indomethacin induced inflammation. Some reports
found that indomethacin increased the expression of HO-1. The authors should
discuss about this point.
(4) Figure4 and Figure5 showed that ZnPP# decreased the expression of HO-1. I
think that ZnPP# inhibit only activity of HO-1. Can ZnPP# decrease the
expression of HO-1?
(5) Figure3C showed that pantoprazole increased the expression of HIF-1.
However, Figure5 showed that pantoprazole decreased HIF-1-#-DNA binding. It
seems contradictory.
(6) The authors think all PPIs may induce HO-1 from the discussion. However,
Yoda et al. (J Physiol Pharmacol. 2010 Jun;61(3):287-94) reported that
lansoprazole, but not omeprazole, induced HO-1. The authors should refer this
paper and discuss about this point.
Minor
(1) There is Figure2E which show the change of DCF-DA fluorescence after
different dosing of pantoprazole. However, in Figure legend, there is no
description of Figure2E. Is Figure2E the part of Figure2D?
(2) In p.8 l.23, the author described “PPI also increased expression of VEGF,
mRNA and protein levels(Figure2A) in RGM-1 gastric mucosal cells.” However,
not Figuer2A but Figure3A showed the expression of VEGF.
(3) In p.9 l.16-18, the author described “Additionally indomethacin challenge
significantly increased the expressions of NADPH oxidase-1(NOX-1) as seen in
Fig.4B”. However, Weston blotting of NOX-1 is shown in Figure4A.
(4) In p.10 l.16, the author described “ICAL-1”. Is it mistake?
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.
Please review this paper.
user
Reviewer's report
Title:Nrf2-mediated heme oxygenase-1 induction of PPI confers adaptive
survival response to NSAID-induced gastric damages
Version: 1Date:30 June 2012
Reviewer: Kazuhide Higuchi
Reviewer's report:
The author reported that pantoprazole can protect stomach against
NSAIDs-induced damages by not only acid suppression but also Nrf2-driven
HO-1 induction which occurs the improvement of NSAIDs-induced ischemia,
attenuation of adhesion molecule, and decreasing inflammatory mediators. This
study is interest. In vitro angiogenesis assay, the author reported that
pantoprazole increase expression of angiogenic factors and activate
NSAIDs-induced angiogenesis. However, there are some problems.
Comments to the author
Major
(1) The author reported that pantoprazole improve NSAIDs-induced ischemia.
However, in this study, although pantoprazole increase expression of angiogenic
factors and activate NSAIDs-induced angiogenesis, it is not enough persuasive
to conclude that pantoprazole improve the ischemia. The authors should discuss
about this point.
(2) In Figure2A, the author demonstrated that Western blots for either cytosolic
keap1 or nuclear Nfr2 in a different time in the presence of 300 M pantoprazole.
However, the author did not describe whether the lower concentration of
pantoprazole could increase cytosolic keap1 and nuclear Nfr2 or not.
(3) Figure4 and Figure5 showed that indomethacin alone did not increase the
expression of HO-1. However, indomethacin induced inflammation. Some reports
found that indomethacin increased the expression of HO-1. The authors should
discuss about this point.
(4) Figure4 and Figure5 showed that ZnPP# decreased the expression of HO-1. I
think that ZnPP# inhibit only activity of HO-1. Can ZnPP# decrease the
expression of HO-1?
(5) Figure3C showed that pantoprazole increased the expression of HIF-1.
However, Figure5 showed that pantoprazole decreased HIF-1-#-DNA binding. It
seems contradictory.
(6) The authors think all PPIs may induce HO-1 from the discussion. However,
Yoda et al. (J Physiol Pharmacol. 2010 Jun;61(3):287-94) reported that
lansoprazole, but not omeprazole, induced HO-1. The authors should refer this
paper and discuss about this point.
Minor
(1) There is Figure2E which show the change of DCF-DA fluorescence after
different dosing of pantoprazole. However, in Figure legend, there is no
description of Figure2E. Is Figure2E the part of Figure2D?
(2) In p.8 l.23, the author described “PPI also increased expression of VEGF,
mRNA and protein levels(Figure2A) in RGM-1 gastric mucosal cells.” However,
not Figuer2A but Figure3A showed the expression of VEGF.
(3) In p.9 l.16-18, the author described “Additionally indomethacin challenge
significantly increased the expressions of NADPH oxidase-1(NOX-1) as seen in
Fig.4B”. However, Weston blotting of NOX-1 is shown in Figure4A.
(4) In p.10 l.16, the author described “ICAL-1”. Is it mistake?
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.
assistant