Reviewer's report
Title:Hepatoprotective role of liver fatty acid binding protein in acetaminophen
induced toxicity
Version: 2Date:12 August 2013
Reviewer: Hartmut Jaeschke
Reviewer's report:
The authors evaluated the potential role of fatty acid binding protein in a cellular
model of acetaminophen toxicity. The findings are novel but a number of issues
need to be addressed:
Major Compulsory Revisions:
1. The authors need to explain what Chang cells are and what the relevance
might be in evaluating APAP toxicity in these cells.
2. Abstract: The authors refer to LDH release as an apoptosis assay. This is
incorrect and needs to be changed.
3. Results and related discussion. The authors argue that an increase in Bax
protein expression is evidence for apoptosis. However, Bax expression is less of
an issue than Bax translocation to the mitochondria. Did FABP1 prevent Bax
translocation to the mitochondria?
4. Even Bax translocation to the mitochondria is not specific for apoptosis. The
role of Bax in acetaminophen-induced cell death (necrosis) has been
investigated (Bajt et al., J Pharmacol Exp Ther. 2008 Jan;324(1):8-14.). In
addition, the authors need to consider that APAP causes necrosis not apoptosis
in mouse hepatocytes in vitro, mouse livers in vivo, in a human hepatocyte cell
line (HepaRG) in vitro and in humans. Thus, it appears highly unlikely that APAP
will cause apoptosis in Chang cells if the mechanism of cell death in this cell line
is relevant for humans.
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 have no competing interests.
Reviewer's report
Title:Hepatoprotective role of liver fatty acid binding protein in acetaminophen
induced toxicity
Version: 2Date:12 August 2013
Reviewer: Hartmut Jaeschke
Reviewer's report:
The authors evaluated the potential role of fatty acid binding protein in a cellular
model of acetaminophen toxicity. The findings are novel but a number of issues
need to be addressed:
Major Compulsory Revisions:
1. The authors need to explain what Chang cells are and what the relevance
might be in evaluating APAP toxicity in these cells.
2. Abstract: The authors refer to LDH release as an apoptosis assay. This is
incorrect and needs to be changed.
3. Results and related discussion. The authors argue that an increase in Bax
protein expression is evidence for apoptosis. However, Bax expression is less of
an issue than Bax translocation to the mitochondria. Did FABP1 prevent Bax
translocation to the mitochondria?
4. Even Bax translocation to the mitochondria is not specific for apoptosis. The
role of Bax in acetaminophen-induced cell death (necrosis) has been
investigated (Bajt et al., J Pharmacol Exp Ther. 2008 Jan;324(1):8-14.). In
addition, the authors need to consider that APAP causes necrosis not apoptosis
in mouse hepatocytes in vitro, mouse livers in vivo, in a human hepatocyte cell
line (HepaRG) in vitro and in humans. Thus, it appears highly unlikely that APAP
will cause apoptosis in Chang cells if the mechanism of cell death in this cell line
is relevant for humans.
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 have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Hepatoprotective role of liver fatty acid binding protein in acetaminophen
induced toxicity
Version: 2Date:12 August 2013
Reviewer: Hartmut Jaeschke
Reviewer's report:
The authors evaluated the potential role of fatty acid binding protein in a cellular
model of acetaminophen toxicity. The findings are novel but a number of issues
need to be addressed:
Major Compulsory Revisions:
1. The authors need to explain what Chang cells are and what the relevance
might be in evaluating APAP toxicity in these cells.
2. Abstract: The authors refer to LDH release as an apoptosis assay. This is
incorrect and needs to be changed.
3. Results and related discussion. The authors argue that an increase in Bax
protein expression is evidence for apoptosis. However, Bax expression is less of
an issue than Bax translocation to the mitochondria. Did FABP1 prevent Bax
translocation to the mitochondria?
4. Even Bax translocation to the mitochondria is not specific for apoptosis. The
role of Bax in acetaminophen-induced cell death (necrosis) has been
investigated (Bajt et al., J Pharmacol Exp Ther. 2008 Jan;324(1):8-14.). In
addition, the authors need to consider that APAP causes necrosis not apoptosis
in mouse hepatocytes in vitro, mouse livers in vivo, in a human hepatocyte cell
line (HepaRG) in vitro and in humans. Thus, it appears highly unlikely that APAP
will cause apoptosis in Chang cells if the mechanism of cell death in this cell line
is relevant for humans.
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 have no competing interests.
assistant