L-CARNITINE AND SOME OF ITS ANALOGS DELAY THE ONSET OF APOPTOTIC CELL-DEATH INITIATED IN MURINE C2.8 HEPATOCYTIC CELLS AFTER HEPATOCYTE GROWTH-FACTOR DEPRIVATION

Addition of L-carnitine and some of its analogs to low-serum incubation medium of murine hepatocytic C2.8 cells prolonged maintenance of life and enhanced cell growth, as compared to controls. The drug acted synergistically with hepatocyte growth factor (HGF). Addition of L-carnitine to cells that had grown confluently in medium supplemented with HGF, significantly delayed the onset of cell death (apoptosis) initiated after HGF deprivation. Protection by L-carnitine was dose-dependent and stereospecific. Similar findings were obtained with three analogs of L-carnitine (i.e. isovaleryl-r-carnitine-HCl, isovaleryl-L-carnitine acid fumarate and butyryl L-carnitine taurine amide). In contrast, four different analogs (i.e. isovareryl-L-carnitine-eptyl-ester-HCl, isovaleryl-L-carnitine-idroxy-butyric-HCl, L-threonyl-L-carnitine-HCl and L-paramethyl-cinnamoil-carnitine-HCl) were inactive. Although the mechanism of cytoprotection stimulated by L-carnitine remains unresolved, the data suggest that this compound serves as a co-factor that influences C2.8 cells to become less susceptible to damaging actions of noxious agents or conditions initiated after HGF withdrawal.