Short‐term treatment with mycophenolic acid increases bile flow in continuously perfused and cold‐preserved rat livers and does not affect hepatic ischemia‐reperfusion injury

摘要: Mycophenolate mofetil (MMF) is a new immunosuppressive agent which has been used successfully after kidney and heart transplantation. Experience with MMF liver transplantation still limited. In particular, there no information about influence on ischemia-reperfusion injury (IRI). Therefore, the aim of this investigation was to assess effects mycophenolic acid (MPA), pharmacologically active metabolite MMF, in cold-preserved or normal rat liver. Livers male Sprague-Dawley rats were subjected cold ischemia University Wisconsin (UW) solution (24 h, 4°C) reperfused for 2 h absence presence MPA (100 μg/ml, n=5–6 each). Another group received pretreatment 20 min prior (n=7). further experiments, livers perfused bile salt-free Krebs-Henseleit buffer continuous fashion (controls, n=5). infused from 20–40 starting perfusion therapeutic concentrations (5 10 40 100 μg/ml; n=3–6 There significant portal pressure nor postischemic efflux rates LDH. resulted improvement flow during reperfusion (0.32±0.05 μl/min × g liver) compared controls (0.17±0.04 liver, mean±SEM). contrast, not influenced by administration period only (0.18±0.07 liver). continuously livers, increased salt-independent (1.00±0.06 dose-dependent manner, reaching half-maximal around 5 μg/ml (1.66±0.15 maximal at (2.61±0.28 conclusion, neither preischemic influences IRI hepatocytes significantly hypothermic preservation UW solution. contrast other agents, exhibits strong choleretic effects, are related stimulation formation.