title: Polydatin protects hepatocytes against mitochondrial injury in acute severe hemorrhagic shock via SIRT1-SOD2 pathway.
abstract: OBJECTIVE
  The aim of the study was to determine whether hepatocyte mitochondrial injury instigates severe shock and to explore effective therapy.
  
  
  METHODS
  Wistar rats were randomly divided into five groups: Control (sham) group, shock + normal saline, shock + cyclosporine A, shock + resveratrol (Res) and shock + polydatin (PD) group. Mitochondrial morphology and function in hepatocytes following treatment were determined.
  
  
  RESULTS
  Hepatocytes following severe shock exhibited mitochondrial dysfunction characterized with opening of mitochondrial permeability transition pores, mitochondrial swelling, decreased mitochondrial membrane potential (ΔΨm) and reduced ATP levels. Moreover, severe shock induced oxidative stress with increased lipid peroxidation and reactive oxygen species, decreased SOD2 (Superoxide Dismutase 2) and GSH/GSSG, which resulted in increased lysosomal membrane permeabilization and hepatocyte mitochondrial injury. Additionally, Res and PD restored decreased deacetylase sirtuin1 activity and protein expression in liver tissue following severe shock, suppressed oxidative stress-induced lysosomal unstability and mitochondrial injury by increasing the protein expression of SOD2, and thereby contributed to the prevention of hepatocyte mitochondria dysfunction and liver injury.
  
  
  CONCLUSIONS
  PD effectively preserved hepatocytes from mitochondrial injury via SIRT1-SOD2 pathway and may be a new approach to treatment of irreversible shock.
authors.affiliation: Southern Medical University, Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology , Guangzhou, 510515 , China +86 20 61648232 ; +86 20 61648299 ; zhaoks@fimmu.com , songrui110@126.com.
authors.forename: Pengyun
authors.initials: P
authors.lastname: Li
authors.forename: Xingmin
authors.initials: X
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Song
authors.forename: Ke-Seng
authors.initials: KS
authors.lastname: Zhao
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D005960:Glucosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000473:pathology*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D016572:Cyclosporine; D005960:Glucosides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D056564:Sirtuin 1; D013267:Stilbenes; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C488368:Sirt1 protein, rat; C058229:polydatin
keywords: hemorrhagic shock; liver; mitochondria protection; polydatin; sirtuin1