Physicochemical and physiological properties of 5alpha-cyprinol sulfate, the toxic bile salt of cyprinid fish

J Lipid Res. 2003 Sep;44(9):1643-51. doi: 10.1194/jlr.M300155-JLR200. Epub 2003 Jun 16.

Abstract

5alpha-Cyprinol sulfate was isolated from bile of the Asiatic carp, Cyprinus carpio. 5alpha-Cyprinol sulfate was surface active and formed micelles; its critical micellization concentration (CMC) in 0.15 M Na+ using the maximum bubble pressure device was 1.5 mM; by dye solubilization, its CMC was approximately 4 mM. At concentrations >1 mM, 5alpha-cyprinol sulfate solubilized monooleylglycerol efficiently (2.1 molecules per mol micellar bile salt). When infused intravenously into the anesthetized rat, 5alpha-cyprinol sulfate was hemolytic, cholestatic, and toxic. In the isolated rat liver, it underwent little biotransformation and was poorly transported (Tmax congruent with 0.5 micromol/min/kg) as compared with taurocholate. 5alpha-Cyprinol, its bile alcohol moiety, was oxidized to its corresponding C27 bile acid and to allocholic acid (the latter was then conjugated with taurine); these metabolites were efficiently transported. 5alpha-Cyprinol sulfate inhibited taurocholate uptake in COS-7 cells transfected with rat asbt, the apical bile salt transporter of the ileal enterocyte. 5alpha-Cyprinol had limited aqueous solubility (0.3 mM) and was poorly absorbed from the perfused rat jejunum or ileum. Sampling of carp intestinal content indicated that 5alpha-cyprinol sulfate was present at micellar concentrations, and that it did not undergo hydrolysis during intestinal transit. These studies indicate that 5alpha-cyprinol sulfate is an excellent digestive detergent and suggest that a micellar phase is present during digestion in cyprinid fish.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bile / chemistry
  • Bile Acids and Salts / chemistry*
  • Bile Acids and Salts / isolation & purification
  • Bile Acids and Salts / metabolism*
  • Bile Acids and Salts / toxicity
  • Biological Transport
  • Biotransformation
  • Carps / metabolism
  • Cell Line
  • Cholestanols / chemistry*
  • Cholestanols / isolation & purification
  • Cholestanols / metabolism*
  • Cholestanols / toxicity
  • In Vitro Techniques
  • Intestinal Mucosa / metabolism
  • Liver / metabolism
  • Molecular Structure
  • Perfusion
  • Rats
  • Spectrometry, Mass, Electrospray Ionization
  • Surface Tension

Substances

  • Bile Acids and Salts
  • Cholestanols
  • anhydrocyprinol