title: 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.
authors.affiliation: Department of Pharmacology, Asahikawa Medical College, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hara
authors.forename: N
authors.initials: N
authors.lastname: Hayase
authors.forename: H
authors.initials: H
authors.lastname: Hashizume
authors.forename: Y
authors.initials: Y
authors.lastname: Abiko
mesh_terms: D000818:Animals; D004109:Dilazep / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects*; D007038:Hypotonic Solutions; D008244:Lysophosphatidylcholines / Q000633:toxicity*; D008297:Male; D008823:Micelles; D010172:Palmitoylcarnitine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C089215:1-palmitoyl-2-lysophosphatidylcholine; D007038:Hypotonic Solutions; C092019:K 7259; D008244:Lysophosphatidylcholines; D008823:Micelles; D014665:Vasodilator Agents; D010172:Palmitoylcarnitine; D004109:Dilazep