Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2015; 21(24): 7468-7477
Published online Jun 28, 2015. doi: 10.3748/wjg.v21.i24.7468
Grape seed proanthocyanidin protects liver against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress
Zhen-Chao Xu, Jie Yin, Bo Zhou, Yu-Ting Liu, Yue Yu, Guo-Qiang Li
Zhen-Chao Xu, Bo Zhou, Yu-Ting Liu, Yue Yu, Guo-Qiang Li, Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Jie Yin, Department of Respiratory Medicine, Jinling Hospital, Nanjing 210002, Jiangsu Province, China
Author contributions: Li GQ and Yu Y designed the research; Xu ZC, Yin J and Zhou B performed the animal and molecular biology experiments; Zhou B and Liu YT analyzed the data; Xu ZC and Yin J wrote the paper.
Supported by The Jiangsu Province Natural Science Fund Subject, No. BK20131445; and the Scientific Research Program of Ministry of Health, No. 201302009.
Ethics approval: The study was reviewed and approved by the Nanjing Medical University Institutional Review Board.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Nanjing Medical University (IACUC protocol number: NJMU08-092).
Conflict-of-interest: There is no conflict of interest in this study.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at liguoqiang@njmu.edu.cn. Participants gave informed consent for data sharing. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Guo-Qiang Li, MD, PhD, Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. liguoqiang@njmu.edu.cn
Telephone: +86-25-83672106 Fax: +86-25-83672106
Received: January 6, 2015
Peer-review started: January 7, 2015
First decision: January 22, 2015
Revised: February 26, 2015
Accepted: April 3, 2015
Article in press: April 3, 2015
Published online: June 28, 2015
Processing time: 173 Days and 18 Hours
Abstract

AIM: To explore the effect of grape seed proanthocyanidin (GSP) in liver ischemia/reperfusion (IR) injury and alleviation of endoplasmic reticulum stress.

METHODS: Male Sprague-Dawley rats (220-250 g) were divided into three groups, namely, sham, IR, and GSP groups (n = 8 each). A liver IR (70%) model was established and reperfused for 6 h. Prior to reperfusion, the GSP group was administered with GSP (100 mg/kg) for 15 d, and liver histology was then investigated. Serum aminotransferase and inflammatory mediators coupled with superoxide dismutase and methane dicarboxylic aldehyde were detected. Western blot was conducted to analyze the expression of glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-κb. Apoptotic cells were detected by TUNEL staining.

RESULTS: The serum aminotransferase, apoptotic cells, and Suzuki scores decreased in the GSP group compared with the IR group (Ps < 0.05). The methane dicarboxylic aldehyde level was decreased in the GSP group, but the superoxide dismutase level was reversed (Ps < 0.05). Similarly, GSP downregulated the proinflammatory factors and upregulated the levels of anti-inflammatory factors (Ps < 0.05). Western blot data showed that GSP increased glucose-regulated protein 78 expression and suppressed expression of CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-κb compared with the IR group.

CONCLUSION: GSP possesses antioxidative, anti-inflammatory, and antiapoptotic effects by relieving endoplasmic reticulum stress through regulation of related signaling pathways to protect the liver against IR injury.

Keywords: Anti-apoptosis; Endoplasmic reticulum stress; Grape seed proanthocyanidin; Inflammation; Ischemia/reperfusion injury

Core tip: Liver ischemia/reperfusion (IR) injury induces endoplasmic reticulum (ER) stress. Numerous studies show that excessive ER stress aggravates IR injury. Grape seed proanthocyanidin (GSP) is an effective protector against IR injury. However, the detailed protective mechanisms remain unclear. Therefore, this study explored the effect of GSP in the liver for protection against IR injury and the alleviation of ER stress. The results indicate that GSP possesses antioxidative, anti-inflammatory, and antiapoptotic effects by relieving ER stress in the liver through regulation of related signaling pathways.