Ischemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury.
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.
Glanemann
Matthias
M
Department of General, Visceral, and Transplantation Surgery, Charité, Campus Virchow Klinikum, Humboldt University Berlin, Berlin, Germany.
Strenziok
Romy
R
Kuntze
Robert
R
Münchow
Simone
S
Dikopoulos
Nektarios
N
Lippek
Frank
F
Langrehr
Jan M
JM
Dietel
Manfred
M
Neuhaus
Peter
P
Nussler
Andreas K
AK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D045304:Cytochromes c / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006358:Hot Temperature; D020287:In Situ Nick-End Labeling; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D019194:Ischemic Preconditioning; D007962:Leukocytes / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D045304:Cytochromes c; D009195:Peroxidase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D008775:Methylprednisolone