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Correspondence/Rebuttal
Response to the letter to the editor from Dr. Hartmut Jaeschke Wei Li, and chen chen J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.7b05975 • Publication Date (Web): 06 Feb 2018 Downloaded from http://pubs.acs.org on February 6, 2018
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Journal of Agricultural and Food Chemistry
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Letter to the editor
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Response to the letter to the editor from Dr. Hartmut Jaeschke
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Wei Li1*, Chen Chen2.
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1
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118 China
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2
School of Biomedical Sciences, University of Queensland, Brisbane 4072, Australia
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Correspondence
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Professor Wei Li, College of Chinese Medicinal Materials, Jilin Agricultural University,
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Changchun 130118, China. E-Mail:
[email protected], Tel. /Fax: +86-431-84533304.
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We read carefully with interest the letter by Dr. Hartmut, commenting on our recent published
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paper in Journal of Agricultural and Food Chemistry about the hepatoprotective effect of
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ginsenoside Rg5 (G-Rg5) on acetaminophen (APAP) -induced liver toxicology1. We thank Dr.
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Hartmut for his comments on the anti-apoptotic effect of natural compounds. We also thank the
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editor for the opportunity to respond to Dr. Hartmut’s comments.
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We acknowledge the fact that the apoptosis during APAP hepatotoxicity is controversial in the
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previous works2. In fact, many researchers have reached different conclusions between hepatic
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necrosis and apoptosis caused by APAP overdoses. Although Dr. Hartmut insisted that there was
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few evidence for caspase-dependent apoptosis in APAP-induced hepatotoxicity3, we did
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demonstrate that APAP-induced liver injury was caused by both apoptosis and necrosis.
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In response to Dr. Hartmut further, we would like to take this opportunity to offer following details:
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We agree with Dr. Hartmut that the activation of caspase is the most significant feature of
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apoptosis in mouse and humans after APAP exposure2. The findings of our work indicated that the
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protein expressions of caspase-3, caspase-8, and caspase-9 were remarkably inhibited after
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ginsenoside Rg5 treatment evidenced by western blotting analysis1. Dr. Hartmut questioned that
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only minor increase in cleaved caspases was observed in APAP toxicity in our results. We
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speculated that ICR mice may be more resilient to APAP toxicity, which was also reported in our
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previous paper4-5. Similar to our results, only 2.2-fold increase in cleaved caspase 3 was observed
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in BALB/ c mice after exposure to APAP with a dose of 400 mg/kg6. Interestingly, the results of
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Bax and cytochrome C support that APAP-induced apoptosis occurs indeed in different animal
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models7-8. Certainly, the demonstrated conclusion on caspase-dependent apoptosis also receives
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support from many other researchers in their published papers9-11.
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Dr. Hartmut also suggested that Bax staining by immunohistochemistry (IHC) was caused by
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unspecific adherence of the secondary antibodies to necrotic tissues. In fact, secondary antibodies
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incubation under the same conditions without first antibodies and for the same incubation period
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in negative controls did not show any staining of liver tissues in our experiment. The results from
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two recent papers by Sun et al., Zhang et al., are in line with us that APAP causes pro-apoptotic
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mitochondrial Bax translocation12-13. Similar to our findings, there is no protein expression of Bax
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in controls evidenced by IHC analysis. 2
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Taken all together, we appreciate the comments from Dr. Hartmut regarding our article. Since
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our results on caspase-dependent apoptosis occurrence during APAP-overdose toxicity is still
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preliminary, more evidences and clear information about the evidence of the apoptosis pathway
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are required to further confirm and clarify the liver-protection mechanism of G-Rg5 or other
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ginsenosides. Meanwhile, we realize that our work is only a part of searching effort for the cellular
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mechanism underlying the clinic observation of beneficial effects of natural compounds. We
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believe that other mechanisms may also be involved in APAP-caused hepatotoxicity.
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Conflicts of interest: The authors have nothing to disclose.
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Reference
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Effect of Ginsenoside Rg5, a Main Rare Ginsenoside, on Acetaminophen-Induced Hepatotoxicity in
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Mice. J Agric Food Chem 2017, 65 (42), 9226-9236.
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Sharma, S.; Singh, R. L.; Kakkar, P., Modulation of Bax/Bcl-2 and caspases by probiotics during
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acetaminophen induced apoptosis in primary hepatocytes. Food Chem Toxicol 2011, 49 (4), 770-9.
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