Reviewer's report
Title:Ozagrel hydrochloride, a selective thromboxane A2 synthase inhibitor,
alleviates liver injury induced by acetaminophen overdose in mice
Version: 2Date:17 October 2012
Reviewer: Svenja Sydor
Reviewer's report:
The manuscript of Tomishima and Ishitsuka et al. concerns with the effect of the
TXA2 synthase inhibitor ozagrel within Acetaminophen/Paracetamol
(APAP)-associated liver injury.
The authors could show that ozagrel-administration ameliorates the outcome of
liver injury after APAP-intoxication explicitly. Mice with ozagrel-injection showed
increased survival rates and were protected from APAP-induced liver damage. In
vitro experiments could show that ozagrel may reduce NAPQI
(N-acetyl-p-benzoquinone imine), a reactive metabolite generated after
APAP-administration. The authors suppose that ozagrel could be applied as
efficient drug to reduce APAP-related liver injury as NAC (N-acetyl cysteine) is
still used as an effective antidote after APAP- intoxication in clinical practice.
The experiments were designed substantially including cell culture experiments
as well as a mouse model. The results are reported in a clear and well-organized
manner with established and qualitative adequate methods and exactness.
Minor comments:
- In figure 5A the definitions of the asterisks shown in this graph are not given in
figure legends which make the diagram incomprehensible. Please change the
figure legend accordingly.
Major comments:
- The authors seek to use ozagrel as effective new treatment in APAP-induced
liver injury because NAC has limited therapeutic efficacy against APAP-induced
hepatoxicity. However in vitro experiments (figure 6) show that NAC shows a
higher efficacy versus NAPQI-induced cell death. How can the authors explain
this issue? What are the advantages of ozagrel- compared to NAC-administration
after APAP-intoxication in the author`s opinion? This question should be
discussed by the authors.
- Did the authors also measure the effect of NAC on hepatic GSH depletion and
compare it to the effect of ozagrel as shown in figure 5A? This could emphasise
the opinion that ozagrel-treatment should be preferred instead of NAC-treatment.
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.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Ozagrel hydrochloride, a selective thromboxane A2 synthase inhibitor,
alleviates liver injury induced by acetaminophen overdose in mice
Version: 2Date:17 October 2012
Reviewer: Svenja Sydor
Reviewer's report:
The manuscript of Tomishima and Ishitsuka et al. concerns with the effect of the
TXA2 synthase inhibitor ozagrel within Acetaminophen/Paracetamol
(APAP)-associated liver injury.
The authors could show that ozagrel-administration ameliorates the outcome of
liver injury after APAP-intoxication explicitly. Mice with ozagrel-injection showed
increased survival rates and were protected from APAP-induced liver damage. In
vitro experiments could show that ozagrel may reduce NAPQI
(N-acetyl-p-benzoquinone imine), a reactive metabolite generated after
APAP-administration. The authors suppose that ozagrel could be applied as
efficient drug to reduce APAP-related liver injury as NAC (N-acetyl cysteine) is
still used as an effective antidote after APAP- intoxication in clinical practice.
The experiments were designed substantially including cell culture experiments
as well as a mouse model. The results are reported in a clear and well-organized
manner with established and qualitative adequate methods and exactness.
Minor comments:
- In figure 5A the definitions of the asterisks shown in this graph are not given in
figure legends which make the diagram incomprehensible. Please change the
figure legend accordingly.
Major comments:
- The authors seek to use ozagrel as effective new treatment in APAP-induced
liver injury because NAC has limited therapeutic efficacy against APAP-induced
hepatoxicity. However in vitro experiments (figure 6) show that NAC shows a
higher efficacy versus NAPQI-induced cell death. How can the authors explain
this issue? What are the advantages of ozagrel- compared to NAC-administration
after APAP-intoxication in the author`s opinion? This question should be
discussed by the authors.
- Did the authors also measure the effect of NAC on hepatic GSH depletion and
compare it to the effect of ozagrel as shown in figure 5A? This could emphasise
the opinion that ozagrel-treatment should be preferred instead of NAC-treatment.
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.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Ozagrel hydrochloride, a selective thromboxane A2 synthase inhibitor,
alleviates liver injury induced by acetaminophen overdose in mice
Version: 2Date:17 October 2012
Reviewer: Svenja Sydor
Reviewer's report:
The manuscript of Tomishima and Ishitsuka et al. concerns with the effect of the
TXA2 synthase inhibitor ozagrel within Acetaminophen/Paracetamol
(APAP)-associated liver injury.
The authors could show that ozagrel-administration ameliorates the outcome of
liver injury after APAP-intoxication explicitly. Mice with ozagrel-injection showed
increased survival rates and were protected from APAP-induced liver damage. In
vitro experiments could show that ozagrel may reduce NAPQI
(N-acetyl-p-benzoquinone imine), a reactive metabolite generated after
APAP-administration. The authors suppose that ozagrel could be applied as
efficient drug to reduce APAP-related liver injury as NAC (N-acetyl cysteine) is
still used as an effective antidote after APAP- intoxication in clinical practice.
The experiments were designed substantially including cell culture experiments
as well as a mouse model. The results are reported in a clear and well-organized
manner with established and qualitative adequate methods and exactness.
Minor comments:
- In figure 5A the definitions of the asterisks shown in this graph are not given in
figure legends which make the diagram incomprehensible. Please change the
figure legend accordingly.
Major comments:
- The authors seek to use ozagrel as effective new treatment in APAP-induced
liver injury because NAC has limited therapeutic efficacy against APAP-induced
hepatoxicity. However in vitro experiments (figure 6) show that NAC shows a
higher efficacy versus NAPQI-induced cell death. How can the authors explain
this issue? What are the advantages of ozagrel- compared to NAC-administration
after APAP-intoxication in the author`s opinion? This question should be
discussed by the authors.
- Did the authors also measure the effect of NAC on hepatic GSH depletion and
compare it to the effect of ozagrel as shown in figure 5A? This could emphasise
the opinion that ozagrel-treatment should be preferred instead of NAC-treatment.
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.
Declaration of competing interests:
I declare that I have no competing interests.
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