Molecular aspects of membrane stabilization by ursodeoxycholate

Abstract

Background: Ursodeoxycholate, used for therapy in biliary liver diseases, prevents bile salt damage in animal experiments. Using isolated red blood cell and both canalicular and basolateral hepatocyte membranes, the present study examined this protective effect. Methods: Membranes were incubated with chenodeoxycholate, with chenodeoxycholate and ursodeoxycholate simultaneously, and first with ursodeoxycholate followed by chenodeoxycholate. Changes in membrane structure were investigated by electron paramagnetic resonance spectroscopy, using different spin labels. Data were confirmed by analysis of membrane lipids and studies with 14C-labeled bile acids. Results: The increase of polarity in the apolar domain of the membrane caused by chenodeoxycholate corresponded to the amount of solubilized lipids. After preincubation with ursodeoxycholate or its conjugates, membrane damage by subsequent chenodeoxycholate incubation was prevented. This effect was caused by binding of ursodeoxycholate in the apolar domain, of its conjugates in the interface of the membrane. Conclusions: Chenodeoxycholate solubilizes membrane lipids and permits water to permeate into plasma membranes. The steroid nucleus of ursodeoxycholate is bound to the apolar domain and that of the conjugates to the interface of the membrane, thus stabilizing membrane structure.