Effects of sizofiran on endotoxin-enhanced cold ischemia-reperfusion injury of the rat liver.
Physiol Res
; 53(4): 431-7, 2004.
Article
in En
| MEDLINE
| ID: mdl-15312003
ABSTRACT
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-alpha (TNF-alpha) 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- 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-alpha cytotoxicity. In conclusion, inhibition of both TNF- 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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reperfusion Injury
/
Sizofiran
/
Cold Temperature
/
Endotoxins
/
Liver
Limits:
Animals
Language:
En
Journal:
Physiol Res
Journal subject:
FISIOLOGIA
Year:
2004
Document type:
Article