Protective effect of FK506 and thromboxane synthase inhibitor on ischemia-reperfusion injury in non-heart-beating donor in rat orthotopic liver transplantation.
The study investigated the possibility of pharmacologically modulating hepatic allograft function from non-heart-beating donors (NHBDs) using male Lewis rats. The donors were divided into 4 groups: Group 1 in which the vehicle was administered, Group 2 in which FK506 (tacrolimus; a powerful immunosuppressive agent) was administered, Group 3 in which OKY046 (a specific thromboxane synthetase inhibitor) was administered and Group 4 in which FK506 and OKY046 were administered. The recipients received orthotopic liver transplantation. The survival rates differed significantly between the recipients that had received liver transplantation from Groups 1 and 4. The serum liver enzyme and inflammatory cytokine concentrations of the recipients which had received liver transplantation from Groups 2, 3 and 4 were significantly lower than those of the recipients that had received liver transplantation from Group 1. Although there was no significant difference, all parameters were better in the recipients that had received transplantation from Group 4 than those that had received transplantation from Groups 2 and 3. The action mechanisms of FK506 and OKY046 are completely different. Therefore, concomitant use of FK506 and OKY046 might have additive effects on liver transplantation from NHBDs. In conclusion, we demonstrated that pretreatment of NHBDs using FK506 and OKY046 ameliorated graft viability.
Department of Digestive Pediatric Surgery, The University of Tokushima School of Medicine, Tokushima, Japan.
Katsuya
K
Sasaki
Hidenori
H
Miyake
Takafumi
T
Kinoshita
Shizuo
S
Ikeyama
Seiki
S
Tashiro
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000293:injuries; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D016559:Tacrolimus / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014019:Tissue Donors; D014184:Transplantation, Homologous
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel; D016559:Tacrolimus