Reviewer's report 
 Antioxidant mechanisms of insulin-like growth factor-I (IGF-I) in rats with advanced liver Title: 
cirrhosis. 
 1  25 October 2004 Version: Date: 
 Jens-Gerd G Scharf Reviewer: 
Reviewer's report: 
The study by Garcia-Fernandez and co-workers aimed to study antioxidant effects of IGF-I 
administration in a rat model of liver cirrhosis. The present study follows previous publications of the authors showing a protective effect of exogenous IGF-I during experimental liver fibrogenesis. Using a rat model of CCl4 inhalation, cirrhotic animals showed increased hepatic levels of iron, copper, 
ferritin, transferrin, myeloperoxidase as well as iNOS production. Treatment of IGF-I resulted in a 
significant reduction of all these parameters. From these data the authors conclude that the beneficial effect of IGF-I treatment during fibrogenesis was associated with a reduction of the “prooxidant” and proinflammatory factors. In general, the results are of potential interest. However, 
several major points need to be addressed. 
1. Major point: In the present manuscript the authors suggest an antioxidant mechanism underlying 
the protective effect of exogenously added IGF-I during experimental liver fibrogenesis. However, 
the authors do not provide any experimental evidence for this conclusion. From the present 
manuscript it is not clear whether IGF-I really acts through antioxidant mechanisms or through other mechanisms which secondarily lead to a reduction of the above mentioned parameters. Therefore, the conclusions drawn from the experimental data in the title, abstract and discussion of the 
manuscript should be carefully revised. In addition, the term “prooxidant” given by the authors is 
misleading and should be deleted from the text. 2. Minor points: In the figure legends the authors state that iron was present in Kupffer cells (Fig. 1) and that a strong iNOS staining was detected in Kupffer cells (Fig. 2), respectively. However, the 
authors provide no experimental evidence clearly identifying KC. Therefore, further experiments are 
necessary such as immunohistology showing a colocalization with Kupffer cells specific immunostaining. 
3. In Fig.1, the Perl´s Prussian Blue staining of the healthy control group should be depicted as well. 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
none 
Reviewer's report 
 Antioxidant mechanisms of insulin-like growth factor-I (IGF-I) in rats with advanced liver Title: 
cirrhosis. 
 1  25 October 2004 Version: Date: 
 Jens-Gerd G Scharf Reviewer: 
Reviewer's report: 
The study by Garcia-Fernandez and co-workers aimed to study antioxidant effects of IGF-I 
administration in a rat model of liver cirrhosis. The present study follows previous publications of the authors showing a protective effect of exogenous IGF-I during experimental liver fibrogenesis. Using a rat model of CCl4 inhalation, cirrhotic animals showed increased hepatic levels of iron, copper, 
ferritin, transferrin, myeloperoxidase as well as iNOS production. Treatment of IGF-I resulted in a 
significant reduction of all these parameters. From these data the authors conclude that the beneficial effect of IGF-I treatment during fibrogenesis was associated with a reduction of the “prooxidant” and proinflammatory factors. In general, the results are of potential interest. However, 
several major points need to be addressed. 
1. Major point: In the present manuscript the authors suggest an antioxidant mechanism underlying 
the protective effect of exogenously added IGF-I during experimental liver fibrogenesis. However, 
the authors do not provide any experimental evidence for this conclusion. From the present 
manuscript it is not clear whether IGF-I really acts through antioxidant mechanisms or through other mechanisms which secondarily lead to a reduction of the above mentioned parameters. Therefore, the conclusions drawn from the experimental data in the title, abstract and discussion of the 
manuscript should be carefully revised. In addition, the term “prooxidant” given by the authors is 
misleading and should be deleted from the text. 2. Minor points: In the figure legends the authors state that iron was present in Kupffer cells (Fig. 1) and that a strong iNOS staining was detected in Kupffer cells (Fig. 2), respectively. However, the 
authors provide no experimental evidence clearly identifying KC. Therefore, further experiments are 
necessary such as immunohistology showing a colocalization with Kupffer cells specific immunostaining. 
3. In Fig.1, the Perl´s Prussian Blue staining of the healthy control group should be depicted as well. 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
none 
Please review this paper.
user
Reviewer's report 
 Antioxidant mechanisms of insulin-like growth factor-I (IGF-I) in rats with advanced liver Title: 
cirrhosis. 
 1  25 October 2004 Version: Date: 
 Jens-Gerd G Scharf Reviewer: 
Reviewer's report: 
The study by Garcia-Fernandez and co-workers aimed to study antioxidant effects of IGF-I 
administration in a rat model of liver cirrhosis. The present study follows previous publications of the authors showing a protective effect of exogenous IGF-I during experimental liver fibrogenesis. Using a rat model of CCl4 inhalation, cirrhotic animals showed increased hepatic levels of iron, copper, 
ferritin, transferrin, myeloperoxidase as well as iNOS production. Treatment of IGF-I resulted in a 
significant reduction of all these parameters. From these data the authors conclude that the beneficial effect of IGF-I treatment during fibrogenesis was associated with a reduction of the “prooxidant” and proinflammatory factors. In general, the results are of potential interest. However, 
several major points need to be addressed. 
1. Major point: In the present manuscript the authors suggest an antioxidant mechanism underlying 
the protective effect of exogenously added IGF-I during experimental liver fibrogenesis. However, 
the authors do not provide any experimental evidence for this conclusion. From the present 
manuscript it is not clear whether IGF-I really acts through antioxidant mechanisms or through other mechanisms which secondarily lead to a reduction of the above mentioned parameters. Therefore, the conclusions drawn from the experimental data in the title, abstract and discussion of the 
manuscript should be carefully revised. In addition, the term “prooxidant” given by the authors is 
misleading and should be deleted from the text. 2. Minor points: In the figure legends the authors state that iron was present in Kupffer cells (Fig. 1) and that a strong iNOS staining was detected in Kupffer cells (Fig. 2), respectively. However, the 
authors provide no experimental evidence clearly identifying KC. Therefore, further experiments are 
necessary such as immunohistology showing a colocalization with Kupffer cells specific immunostaining. 
3. In Fig.1, the Perl´s Prussian Blue staining of the healthy control group should be depicted as well. 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
none 
assistant