title: Protective effects of combined ischemic preconditioning and ascorbic acid on mitochondrial injury in hepatic ischemia/reperfusion.
abstract: BACKGROUND
  This study examined the in vivo effects of ischemic preconditioning (IPC), ascorbic acid (AA), or a combination (IPC + AA) on the level of mitochondrial injury caused by hepatic ischemia/reperfusion (I/R).
  
  
  METHODS
  A rat liver was preconditioned with 10 min of ischemia followed by 10 min of reperfusion, and then subjected to 90 min of ischemia followed by 5 h of reperfusion. The rats were pretreated with AA (100 mg/kg, i.v.) 5 min before the sustained ischemia.
  
  
  RESULTS
  I/R increased the aminotransferase activity and level of mitochondrial lipid peroxidation, whereas it decreased the reduced glutathione:oxidized glutathione ratio. Either the IPC or AA pretreatment alone attenuated these changes, with the effect being enhanced by IPC + AA. The level of mitochondrial glutamate dehydrogenase, which is specifically located in the matrix, decreased after I/R but this was prevented by IPC + AA. Significant peroxide production was observed after 10 min of reperfusion after sustained ischemia. This change was attenuated by either IPC or AA alone and was further attenuated by IPC + AA. The mitochondria isolated after I/R were rapidly swollen, indicating an opening of the permeability transition pore. However, this was markedly reduced by IPC + AA. The hepatic ATP level was lower after I/R, which was restored by IPC alone and IPC + AA.
  
  
  CONCLUSIONS
  Our findings suggest that IPC and AA synergistically reduce the level of mitochondrial damage during I/R as a result of decreased postischemic oxidant stress.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Woo-Yong
authors.initials: WY
authors.lastname: Lee
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005969:Glutamate Dehydrogenase / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D000975:Antioxidants; D010545:Peroxides; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D001205:Ascorbic Acid