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 incubatio n medium of murine hepatocytic C2.8 cells prolonged maintenance of lif e and enhanced cell growth, as compared to controls. The drug acted sy nergistically with hepatocyte growth factor (HGF). Addition of L-carni tine to cells that had grown confluently in medium supplemented with H GF, significantly delayed the onset of cell death (apoptosis) initiate d 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-carnitin e acid fumarate and butyryl L-carnitine taurine amide). In contrast, f our different analogs (i.e. isovareryl-L-carnitine-eptyl-ester-HCl, is ovaleryl-L-carnitine-idroxy-butyric-HCl, L-threonyl-L-carnitine-HCl an d L-paramethyl-cinnamoil-carnitine-HCl) were inactive. Although the me chanism of cytoprotection stimulated by L-carnitine remains unresolved , the data suggest that this compound serves as a co-factor that influ ences C2.8 cells to become less susceptible to damaging actions of nox ious agents or conditions initiated after HGF withdrawal.