Prednisolone suppresses ischemia-reperfusion injury of the rat liver by reducing cytokine production and calpain mu activation.
BACKGROUND
We investigated the effects of prednisolone on cytokine production and calpain mu activation during hepatic ischemia-reperfusion (IR) injury.


METHODS
The hilar area of the left lateral and median lobes of rat liver was clamped for 60 min. Prednisolone was administered at 1.0, 3.0, or 10 mg/kg at 30 min before ischemia. In addition to biochemical and microscopic analyses, IL-beta and TNF-alpha production was evaluated by RT-PCR. Calpain mu activation and talin degradation were determined by Western blotting, using specific antibodies.


RESULTS
In the control and prednisolone (1.0 mg/kg) groups, serum AST and ALT levels were elevated, and cell membrane bleb formation was observed after 2 h of reperfusion. Moreover, calpain mu activation, talin degradation, and overexpression of IL-beta and TNF-alpha mRNAs were detected. Infusion of prednisolone at 3.0 or 10 mg/kg significantly suppressed biochemical and microscopic changes. At 10 mg/kg, prednisolone markedly suppressed IL-beta and TNF-alpha transcription and calpain mu activation and talin degradation, consistent with the improved 7-day survival after total hepatic ischemia (75% vs. 25% in control group, P = 0.039).


CONCLUSIONS
Cytoprotective effect of prednisolone in hepatic IR injury was closely associated with suppression of IL-beta/TNF-alpha production and calpain mu activation.
Department of Surgery and Clinical Oncology, Osaka University Medical School, Suita, Japan.
M
M
Wang
M
M
Sakon
K
K
Umeshita
M
M
Okuyama
K
K
Shiozaki
H
H
Nagano
K
K
Dohno
S
S
Nakamori
M
M
Monden
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001483:Base Sequence; D002154:Calpain / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016608:Talin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D016608:Talin; D014409:Tumor Necrosis Factor-alpha; D011239:Prednisolone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002154:Calpain