Trimetazidine ameliorates the hepatic injury associated with ischaemia-reperfusion in rats

Ischaemia-reperfusion induces structural and functional damage to hepatocytes. The purpose of this study was to evaluate the protective effect of trimetazidine, an antiischaemic drug, in a rat liver model of ischaemia-reperfusion. Male Wistar rats were divided into groups pretreated with different doses of trimetazidine (1, 5, 10 or 20 mg kg(-1) day(-1)) or saline for 7 days. Liver ischaemia was induced for 120 min and blood reflow was subsequently restored for 30, 60, 90 or 120 min. The activities of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) as well as the bile flow and the liver ATP content were determined. Ischaemia-reperfusion induced major alterations of hepatic functions involving increases of ASAT and ALAT activities, a drop of ATP content and a sharp decrease in bile flow. Trimetazidine pretreatment reduced the liver injury. Indeed, it lowered the increase in ALAT and ASAT activities observed immediately after reperfusion and maintained higher concentrations of hepatic ATP. Simultaneously, bile flow was increased. These effects were dose-dependent and 5 mg kg(-1) day(-1) seemed to be the lowest effective dose. In this experimental model trimetazidine pretreatment reduced the liver damage induced by ischaemia-reperfusion. Our data suggest that trimetazidine may be a useful drug in liver surgery to prevent ischaemia-reperfusion injury. (C) 1999 The Italian Pharmacological Society.