Ischemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury

Surgery. 2004 Feb;135(2):203-14. doi: 10.1016/j.surg.2003.08.011.

Abstract

Background: Ischemic preconditioning (I/P) and methylprednisolone (MP) have been suggested to protect against ischemia-reperfusion (IR) injury, which results in an increased tolerance against organ hypoxia.

Methods: Before 45 minutes of hepatic ischemia, male Wistar rats were pretreated with either I/P (5/30 minutes) or MP (30 mg/kg BW). The degree of IR injury and the postischemic inflammatory (leukocyte infiltration, myeloperoxidase, intercellular adhesion molecule-1) and apoptotic (TUNEL, caspase 3, cytochrome C) activity was measured in both groups and compared with non-pretreated (ischemic) animals.

Results: Histology and enzyme release revealed that I/P and MP treatment provided significant protection as compared with ischemic controls. TUNEL-positive cells, as well as caspase 3 and cytochrome C expression, were clearly reduced in hepatic tissue of MP-treated animals and partially reduced in I/P-treated animals when compared with ischemic animals. The inflammatory response was considerably reduced in MP- and I/P-treated animals, especially in the early period after ischemia. NF-kappaB/Rel-binding activity was increased after I/P and decreased in MP-treated animals, whereas ischemic controls showed a constant binding activity.

Conclusions: MP (probably by downregulation of NF-kappaB-binding activity) and I/P attenuated the postischemic apoptotic and inflammatory response. Both treatments equally reduced IR-related hepatocellular damage, and, thus, may also be applied equally in surgery involving warm organ hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis
  • Caspase 3
  • Caspases / genetics
  • Cytochromes c / genetics
  • Gene Expression Regulation / drug effects
  • Hot Temperature
  • In Situ Nick-End Labeling
  • Intercellular Adhesion Molecule-1 / genetics
  • Ischemic Preconditioning*
  • Leukocytes / pathology
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Methylprednisolone / pharmacology*
  • NF-kappa B / metabolism
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology*

Substances

  • Anti-Inflammatory Agents
  • NF-kappa B
  • Intercellular Adhesion Molecule-1
  • Cytochromes c
  • Peroxidase
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Methylprednisolone