The mitigating effects of phosphatidylcholines on bile salt- and lysophosphatidylcholine-induced membrane damage.
The effects, at pH 7.0, of a series of 0.2 mM phosphatidylcholines (PC), namely dicaproyl-PC (DCPC), didecanoyl-PC (DDPC), dilauroyl-PC (DLaPC), dimyristoyl-PC (DMPC), dipalmitoyl-PC (DPPC), dioleoyl-PC (DOPC) and dilinoleoyl-PC (DLPC) and a series of 0.2 mM fatty acid salts (namely sodium myristate, palmitate, stearate, oleate and linoleate) upon the erythrocyte haemolysis induced by 2 mM sodium taurodeoxycholate (STDC) were determined. The influence of egg PC and dihexadecyl phosphate (DHDP) concentration upon the haemolysis induced by 1.4 mM sodium deoxycholate (SDC), 2 mM STDC and 0.1 mM lysophosphatidylcholine (LPC) were also established. A bile salt:egg PC mole ratio of 0.5 virtually abolished the haemolysis induced by SDC and STDC, whereas the same ratio of LPC:egg PC only reduced haemolysis from 65 to 40% (maximum haemolysis). DHDP had no effect on the haemolytic action of SDC or STDC. The salts of the fatty acids were non-haemolytic, and when mixed with STDC did not affect the level of haemolysis induced by the bile salt. In contrast, DDPC and DLaPC enhanced the haemolysis of STDC and DCPC had no effect, whereas DMPC, DPPC, DSPC, DOPC, DLPC and egg PC all reduced haemolysis. Maximum reduction was determined for DMPC and egg PC. The mixed micelle preparation temperature (either room or 60 degrees C) and temperature of incubation (either 20 degrees C for 30 min or 37 degrees C for 5 min) had only minor effects on the net haemolysis induced by STDC. These findings may be of significance in understanding the aetiology of certain gastrointestinal diseases and in determining whether mixed bile salt micelles have a role as drug penetration enhancers.
Chelsea Department of Pharmacy, King's College London, UK.
L M
LM
el-Hariri
C
C
Marriott
G P
GP
Martin
D001647:Bile Acids and Salts / Q000633:toxicity*; D004910:Erythrocyte Membrane / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000633:toxicity*; D010713:Phosphatidylcholines / Q000494:pharmacology*
D001647:Bile Acids and Salts; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines