Tumor necrosis factor-α antisense transfer remarkably improves hepatic graft viability

Tomoharu Yoshizumi, Yoshikazu Yonemitsu, Yasuhiro Ikeda, Yasufumi Kaneda, Katsuhiko Yanaga, Keizo Sugimachi, Katsuo Sueishi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Cold ischemia/reperfusion injury of the hepatic graft, an unsolved problem in liver transplantations, is attributed to the release of inflammatory cytokines, especially the tumor necrosis factor- (TNF) α, from activated Kupffer cells (KC). Therefore, the specific inhibition of TNF-α could improve the viability of the hepatic graft upon reperfusion.: We assessed the efficacy of TNF-α antisense (TNF-AS) oligodeoxynucleotides (ODNs) delivery to KC in a rodent liver transplantation model. Results: Seventy-one percent of the animals that received 6 hours preserved grafts in baths of lactated Ringer's solution (4°C) and were treated with TNF-AS survived for over 14 days. Eighty percent of the animals treated with vehicle, sense ODNs, or balanced salt saline (BSS) died. Four hours after reperfusion of the liver, a significant reduction was noted in livers treated with TNF-AS in the release of cytosolic enzymes from the hepatocytes and the serum TNF-α (P<0.05). The expressions of TNF-α on KC and of intercellular adhesion molecule-1 on sinusoidal endothelial cells were completely suppressed in TNF-AS-treated livers. Conclusions: TNF-AS delivery improves the viability of the hepatic graft, and this technique may solve hepatic graft nonfunction in a clinical setting.

Original languageEnglish
Pages (from-to)451-456
Number of pages6
JournalLiver International
Volume26
Issue number4
DOIs
Publication statusPublished - May 1 2006

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Tumor Necrosis Factor-alpha
Transplants
Liver
Kupffer Cells
Oligodeoxyribonucleotides
Liver Transplantation
Reperfusion
Cold Ischemia
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1
Reperfusion Injury
Baths
Hepatocytes
Rodentia
Endothelial Cells
Salts
Cytokines
Enzymes
Serum

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Tumor necrosis factor-α antisense transfer remarkably improves hepatic graft viability. / Yoshizumi, Tomoharu; Yonemitsu, Yoshikazu; Ikeda, Yasuhiro; Kaneda, Yasufumi; Yanaga, Katsuhiko; Sugimachi, Keizo; Sueishi, Katsuo.

In: Liver International, Vol. 26, No. 4, 01.05.2006, p. 451-456.

Research output: Contribution to journalArticle

Yoshizumi, Tomoharu ; Yonemitsu, Yoshikazu ; Ikeda, Yasuhiro ; Kaneda, Yasufumi ; Yanaga, Katsuhiko ; Sugimachi, Keizo ; Sueishi, Katsuo. / Tumor necrosis factor-α antisense transfer remarkably improves hepatic graft viability. In: Liver International. 2006 ; Vol. 26, No. 4. pp. 451-456.
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AU - Sugimachi, Keizo

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