Graft preconditioning with low-dose tacrolimus (FK506) and nitric oxide inhibitor (AGH) reduces ischemia/reperfusion injury after liver transplantation in the rat

Background/Aim: Ischemia/reperfusion (I/R) injury is a main cause of primary dysfunction or non-function after liver transplantation (LTx). Recent evidence indicates that an increase in nitric oxide (NO) production after LTx is associated with I/R injury. The aim of this study was to demonstrate that low-dose FK506 in combination with aminoguanidine (AGH), which leads to a reduction of NO levels, has a protective effect by reducing I/R associated injury after LTx. Materials and methods: Forty-one DA-(RT1av1) rats served as donors and recipients for syngenic orthotopic arterialised LTx. They were divided into 4 groups: controls without pre-/treatment (I), pre-/treatment with high-dose FK506 (II), pre-/treatment with AGH only (III), and pre-/treatment with low-dose FK506 in combination with AGH (IV). After LTx the laboratory parameters and liver biopsy were performed. Results: The levels of transaminase (ALT) in groups I, II and III were significantly higher on day 3 after LTx compared to group IV (p= 0.001, p= 0.001, p= 0.000). In group IV the I/R-associated liver necrosis rate was reduced significantly. Conclusion: Our results demonstrated that a combined dual pharmacological pretreatment (group IV) reduced I/R injury of the graft after LTx in a rat model.