Membrane damage by bile salts: the protective function of phospholipids.

Abstract

The direct toxicity of sodium deoxycholate (SDC) and lysophosphatidylcholine (LPC) to biological membranes was assessed by measurement of goldfish overturn time. When phosphatidylcholine (PC) was incorporated into the aqueous media, the toxicity of both SDC and LPC was reduced, as indicated by increased overturn time. Fish were also pretreated for various times in media containing (a) 1 mM SDC and (b) 1 mM SDC with 1 mM PC. Subsequent transfer to solution, 100 mg litre-1 quinalbarbitone sodium showed that reciprocal overturn times for fish treated using method (a) increased linearly with duration of pretreatment up to a limiting value, obtained after 20 min exposure; 40 min exposure to 1 mM SDC was directly toxic. Fish pretreated using regimen (b) survived longer when challenged with barbiturate, and the reciprocal overturn times were a linear function of time of pretreatment up to at least 40 min. PC also provided protection against membrane damage caused by the synthetic surfactant sodium dodecyl sulphate. Mixed micelle formation between PC and surfactant is thought to account for the protective effects. The results are of significance in the consideration of reflux hypothesis for the aetiology of gastric ulceration and also the possible formulation of drug delivery systems intended to enhance absorption whilst minimizing gastrointestinal damage.