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Protective effects of combined ischemic preconditioning and ascorbic acid on mitochondrial injury in hepatic ischemia/reperfusion.

AbstractBACKGROUND:
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).
MATERIALS AND 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.
AuthorsWoo-Yong Lee, Jun-Seok Lee, Sun-Mee Lee
JournalThe Journal of surgical research (J Surg Res) Vol. 142 Issue 1 Pg. 45-52 (Sep 2007) ISSN: 0022-4804 [Print] United States
PMID17559880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Peroxides
  • Reactive Oxygen Species
  • Malondialdehyde
  • Glutamate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione
  • Ascorbic Acid
Topics
  • Alanine Transaminase (blood)
  • Animals
  • Antioxidants (therapeutic use)
  • Ascorbic Acid (therapeutic use)
  • Aspartate Aminotransferases (blood)
  • Energy Metabolism (drug effects, physiology)
  • Glutamate Dehydrogenase (blood)
  • Glutathione (metabolism)
  • Ischemic Preconditioning (methods)
  • Liver (injuries, metabolism, pathology)
  • Male
  • Malondialdehyde (metabolism)
  • Mitochondria, Liver (drug effects, metabolism, physiology)
  • Oxidative Stress (drug effects)
  • Peroxides (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species (metabolism)
  • Reperfusion Injury (metabolism, pathology, therapy)

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