title: Grape seed proanthocyanidin protects liver against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Zhen-Chao
authors.initials: ZC
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D056604:Grape Seed Extract / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D018836:Inflammation Mediators; D044945:Proanthocyanidins
keywords: Anti-apoptosis; Endoplasmic reticulum stress; Grape seed proanthocyanidin; Inflammation; Ischemia/reperfusion injury