title: Protective effect of grape seed proanthocyanidins against liver ischemic reperfusion injury: particularly in diet-induced obese mice.
abstract: BACKGROUND
  Hepatic ischemia and reperfusion injury (IRI) is a major complication in liver surgery, and hepatic steatosis is a primary factor aggravating cellular injury during IRI. Both pro-inflammatory cytokines and reactive oxygen species (ROS) are key mediators of hepatic IRI. Ischemic preconditioning (IpreC), remote ischemia preconditioning (RIPC) and ischemic postconditioning (IpostC) have offered protections on hepatic IRI, but all these methods have their own shortcomings. Grape seed proanthocyanidins (GSP) has a broad spectrum of pharmacological properties against oxidative stress. Thus, GSP has potential protective effects against hepatic IRI.
  
  
  METHODS
  C57BL/6 mice suffering 30mins hepatic ischemia process were sacrificed after 1h reperfusion to build murine warm hepatic IRI model. The mice were injected GSP intraperitoneally 10, 20, 40mg/kg/day for 3 weeks as pharmacological preconditioning. Obese mice fed with high-fat diet for 24 weeks before used. Three pathways related to IRI, including ROS elimination, pro-inflammatory cytokines release and hypoxia responses were examined.
  
  
  RESULTS
  Our data show that GSP could significantly reduce hepatic IRI by protecting hepatocyte function and increasing the activity of ROS scavengers, as well as decreasing cytokines levels. At the same time, GSP also enhance the hypoxia tolerance response. Combined GSP and postconditioning can provided synergistic protection. In the obese mice suffering hepatic IRI group, GSP was more effective than postconditioning on protecting liver against IRI, and the combined strategy was obviously superior to the solo treatment.
  
  
  CONCLUSIONS
  GSP could protect liver against IRI: particularly in high-fat diet induced obese mice. GSP used as pharmacological preconditioning and combined with other protocols have huge potential to be used in clinical.
authors.affiliation: Key Laboratory of Medical Cell Biology, China Medical University, Shen Yang City, LiaoNing Province, China. xysong@mail.cmu.edu.cn
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Song
authors.forename: Hongde
authors.initials: H
authors.lastname: Xu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Feng
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Li
authors.forename: Meina
authors.initials: M
authors.lastname: Lin
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
mesh_terms: D000818:Animals; D001835:Body Weight; D015687:Cell Hypoxia; D059305:Diet, High-Fat; D016166:Free Radical Scavengers / Q000378:metabolism; D056604:Grape Seed Extract / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D057775:Ischemic Postconditioning / Q000379:methods; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D053583:Interleukin-1beta; D044945:Proanthocyanidins; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha
keywords: Grape seed proanthocyanidins; ischemia; postconditioning; preconditioning; reperfusion injury.