Proanthocyanidins Antagonize Arsenic-Induced Oxidative Damage and Promote Arsenic Methylation through Activation of the Nrf2 Signaling Pathway
Authors: Haixia Wang
Yunhua Hu
Shugang Li
Gangling Feng
Qiang Niu
Mengchuan Xu
Journal: Oxidative Medicine and Cellular Longevity (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Grape seed proanthocyanidin extract; oxidative damage; arsenic methylation; Nrf2; L-02 cells
Affiliations: Department of Public Health, Medical College, Shihezi University, 832000 Xinjiang, China.

Abstract:  Purpose: To investigate the effects of grape seed proanthocyanidin extract (GSPE) on oxidative damage and arsenic (As) methylation and to clarify the role of Nrf2 in the process. Methods: L-02 cells were treated with arsenic (25 ŒºM) and GSPE (10, 25, and 50 mg/L) for 24 h. Cell viability was analyzed by MTT assay. Cell apoptosis and ROS fluorescence were detected by flow cytometry. Oxidative stress marker levels were measured using commercial kits. mRNA and protein expression were detected by qRT-PCR and western blotting. The cellular concentrations of methylation products were measured by HPLC-HGAFS. Arsenic methylation ability of cells was determined. Results: Cell survival rate was significantly lower in the As group than in the control group (P &lt; 0.05), while cell apoptosis increased and the number of apoptotic cells decreased gradually after GSPE intervention. Superoxide dismutase, glutathione, and sulfhydryl levels in the intervention group were significantly higher (P &lt; 0.05), while MDA and ROS levels were significantly lower (P &lt; 0.05) than those in the As group. The mRNA and protein expression of Nrf2, HO-1, NQO1, and glutathione-S-transferase increased in the As + GSPE group compared with that in the As group (P &lt; 0.05). GSPE significantly increased methylated As level, primary methylation index, secondary methylation index, average growth rate of methylation, and average methylation speed compared with the GSPE untreated group (P &lt; 0.05). After Nrf2 inhibition, the effect of GSPE decreased significantly. Conclusion: GSPE activates the Nrf2 signaling pathway to antagonize As-induced oxidative damage and to promote As methylation metabolism. Therefore, GSPE may be a potential agent for relieving As-induced hepatotoxicity. 

Retracted: Yes

PubPeer comments:
 Much more similar than you can expect. Within Figure 2, there appears to be Much More Similar than you can expect between image (D) and image (E). The inverted picture with red boxes is provided to highlight the same part. I would appreciate pubpeer readers comments on this.   , 
 In this paper, see the below picture (figure 3 in the original paper), the protein bands of the same molecular weight are shown in the same color arrows. **The data which gets from the same band of the u00df-actin as control is doubtful**. The authors should be requested to provide original pictures to prove that they did not misuse or adjust the data.  , 
 Noticeably, the band of GG is the same as the band of HJT in the author s dissertation for a Master s degree. Would the authors explain why they edited the picture of western blotting, even changed the label of the band, and when published in the journal deleted the data of HJT? The same parts are shown in the rectangles of the same color.  , 
 The paper has undergone a stealth revision or correction, replacing Figure 2E criticized in the comments above.  The version currently provided on the journal website was created modified on 14 Feb, 2020.  It grieves me to report that Fig 2 still has duplicated pictures, see A and D as below.  The original version (created on 9 April 2016) is still accessible through a copy archived at ResearchGate. , 
 The paper has undergone a **second stealth revision**, replacing Figure 2-A in the comments above. [](http: ) http: www.journaltcm.com index.php Journal display sid 2493  The authors gave the apoptosis rates, 17.41% u00b1 1.88% in c-JNK inhibitor group (as shown in Fig2-E), whereas 10.16% u00b1 1.83% in control group (as shown in Fig2-A). Should the authors find another figure to take the place of Fig2-E, which seems less stained with yellow, compared with Fig A?  ,