Effects of Sizofiran on
Endotoxin-Enhanced Cold Ischemia-Reperfusion Injury of the Rat
M. KUKAN, Z. SZATMÁRY, M. LUTTEROVÁ, D. KUBA, K. VAJDOVÁ, J.
Laboratory of Perfused Organs, SCOT, Institute of Preventive and
Clinical Medicine, Bratislava, Slovak Republic
Received June 25, 2003
Accepted October 3, 2003
Kupffer cells (KC), resident macrophages of the liver, have been
strongly implicated in lipopolysaccharide (LPS)-induced liver
graft injury. However, our recent study showed that sizofiran
(schizophyllan glucan) (SPG), which activates KC, did not
influence cold ischemia-reperfusion liver injury of LPS-exposed
rats. Here we investigated some mechanisms by which SPG does not
aggravate LPS-enhanced cold ischemia-reperfusion rat liver
injury. Control and SPG-treated rats were exposed to LPS for 2 h
prior to hepatectomy. The livers were cold-preserved in
University of Wisconsin solution followed by reperfusion with
Krebs-Henseleit buffer. We found that SPG dramatically inhibited
LPS-induced increases of tumor necrosis factor-α
(TNF-α) in the plasma and bile in vivo.
Moreover, LPS-induced TNF- release into the washout solution
after cold ischemia was also abrogated by SPG pretreatment.
However, SPG increased TNF-α release into
the perfusate after reperfusion. On the other hand, SPG
completely abolished expression of c-myc protooncogene, which is
known to sensitize cells to TNF-α
cytotoxicity. In conclusion, inhibition of both TNF-α
release after LPS challenge and c-myc expression may explain why
activation of KC with SPG does not aggravate endotoxin-enhanced
cold ischemia-reperfusion liver injury.
Liver • Cold ischemia-reperfusion • Kupffer cells • Sizofiran
(Schizophyllan glucan) • Tumor necrosis factor-α