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

Ischaemia-reperfusion induces structural and functional damage to hepatocyt es. The purpose of this study was to evaluate the protective effect of trim etazidine, an antiischaemic drug, in a rat liver model of ischaemia-reperfu sion. Male Wistar rats were divided into groups pretreated with different d oses of trimetazidine (1, 5, 10 or 20 mg kg(-1) day(-1)) or saline for 7 da ys. Liver ischaemia was induced for 120 min and blood reflow was subsequent ly restored for 30, 60, 90 or 120 min. The activities of alanine aminotrans ferase (ALAT) and aspartate aminotransferase (ASAT) as well as the bile flo w 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. Trime tazidine pretreatment reduced the liver injury. Indeed, it lowered the incr ease 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) s eemed to be the lowest effective dose. In this experimental model trimetazi dine 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 Pharmacologi cal Society.