Effects of Sizofiran on Endotoxin-Enhanced Cold Ischemia-Reperfusion Injury of the Rat Liver

Title:

Effects of Sizofiran on Endotoxin-Enhanced Cold Ischemia-Reperfusion Injury of the Rat Liver

Creator:

Kukan, M., Szatmáry, Z., Lutterová, M., Kuba, D., Vajdová, K., and Horecký, J.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:caa095eb-375b-4fae-a7e5-09606452386c
uuid:caa095eb-375b-4fae-a7e5-09606452386c

Subject:

Liver, Cold ischemia-reperfusion, Kupffer cells, Sizofiran (Schizophyllan glucan), Tumor necrosis factor-α, and c-myc protooncogene

Type:

article, model:article, and TEXT

Description:

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.

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2004 Volume:53 | Number:4

Harvested from:

CDK

Metadata only:

false