Protective effect of FK506 against ischemia-reperfusion injury of the liver, and especially on the hepatic microcirculation and release of endothelin-1

FK506 has been clarified to have a protective effect against ischemia-reperfusion injury of the liver. The mechanism of the protective effect was experimentally investigated by noting its influence on the hepatic microcircuration and release of tumor necrosis factor (TNF) and endothelin-1 (ET-1). Partial (70%) hepatic ischemia models were prepared under Nembutal anesthesia in the control group and FK506 preadministration group (1.0mg/kg/day was intramuscally administrated for 4 days). Reperfusion was followed by 90min of warm ischemia, and the 24-hour survival rate, hepatic tissue blood flow, mean arterial blood pressure, blood biochemistry values, serum TNF and ET 1 levels, arterial ketone body ratio (AKBR), and histological findings were investigated. The study demonstrated : 1) The 24-hour survival rate, hepatic tissue blood flow, serum GPT level, AKBR, and histological findings were improved by the preadministration of FK506, as compared with the control group; 2) the increase of the blood ET-1 and TNF levels caused by ischemia reperfusion injury of liver mere suppressed immediately after reperfusion by the preadministration of FK506. These results suggests that the protective effect of FK506 against ischemia reperfusion injury of liver is attributable to suppressed ET-1 and TNF levels and improvement of the hepatic microcircuration,