Protective Effects of Dilazep and its Derivative K-7259 on the Haemolysis Induced by Amphiphiles in Rat Erythrocytes

Abstract

The effects of dilazep and K-7259, a dilazep derivative, on the haemolysis (as evidenced by release of haemoglobin) induced by palmitoyl-L-carnitine (PAL-CAR) or palmitoyl 1-alpha-lysophosphatidylcholine (PAL-LPC) have been determined in rat erythrocytes. At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced haemolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haemolysis were approximately 13 and 14 microM, respectively. The 50% haemolysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 microM) but not at the highest concentration used (1 mM). K-7259 attenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentrations ranging from 1 microM to 1 mM. Similarly, dilazep (1 to 100 microM) and K-7259 (1 microM to 1 mM) significantly or insignificantly attenuated the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC. Neither dilazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor, at concentrations of 1 and 10 microM, did they attenuate the haemolysis induced by osmotic imbalance (hypotonic haemolysis). These results suggest that both dilazep and K-7259 protect the erythrocyte membrane from the damage induced by PAL-CAR or PAL-LPC. The protective effects of dilazep and K-7259 are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.

Ethanol delays and reverses lysophosphatidylcholine-induced calcium overload in neonatal rat heart cells

“…If its concentration exceeds the CMC, it can form small micelles composed of approximately 180 molecules [28]. Reported CMC values for LPC are highly variable, covering the range 4-300 µM at room temperature [3,14,15,16,26]. Some of this variation may be due to detection limits of the methods or the tendency of LPC to form larger micelles as the concentration increases [14].…”

K‐7259: A Cardioprotective Derivative of Dilazep

“…10) (18). Nevertheless, neither dilazep (100 ~LM) nor K-7259 (100 pM) affects micelle formation of LPC or palmitoyl carnitine (the critical micelle concentrations for either LPC and palmitoyl carnitine is about 4 pM), indicating that there is no direct interaction of dilazep or K-7259 with LPC or palmitoyl carnitine (IS).…”