PROTECTIVE EFFECTS OF DILAZEP AND ITS DERIVATIVE K-7259 ON THE HEMOLYSIS INDUCED BY AMPHIPHILES IN RAT ERYTHROCYTES

The effects of dilazep and K-7259, a dilazep derivative, an the haemol ysis (as evidenced by release of haemoglobin) induced by palmitoyl-L-c arnitine (PAL-CAR) or palmitoyl 1-alpha-lysophosphatidylcholine (PAL L PC) have been determined in rat erythrocytes. At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced ha emolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haem olysis were approximately 13 and 14 mu M, respectively. The 50% haemol ysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 mu M) but not at the highest concentration used (1 mM), K-7259 at tenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentra tions ranging from 1 mu M to 1 mM. Similarly, dilazep (1 to 100 mu M) and K-7259 (1 mu M to 1 mM) significantly or insignificantly attenuate d the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC, Neither di lazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor , at concentrations of I and 10 mu M, did they attenuate the haemolysi s induced by osmotic imbalance (hypotonic haemolysis). These results s uggest that both dilazep and K-7259 protect the erythrocyte membrane f rom the damage induced by PAL-CAR or PAL-LPC. The protective effects o f dilazep and K-7259 are mediated by same mechanism other than prevent ion of micelle formation or protection of the erythrocyte membrane aga inst osmotic imbalance.