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Tumor necrosis factor‐a antisense transfer remarkably improves hepatic graft viability
Author(s) -
Yoshizumi Tomoharu,
Yonemitsu Yoshikazu,
Ikeda Yasuhiro,
Kaneda Yasufumi,
Yanaga Katsuhiko,
Sugimachi Keizo,
Sueishi Katsuo
Publication year - 2006
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2006.01252.x
Subject(s) - tumor necrosis factor alpha , medicine , liver transplantation , reperfusion injury , transplantation , necrosis , saline , viaspan , viability assay , sense (electronics) , ischemia , pharmacology , cell , chemistry , biochemistry
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. Methods: 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.