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

Abstract

5 ␣ -Cyprinol sulfate was isolated from bile of the Asiatic carp, Cyprinus carpio . 5 ␣ -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 ‫ف‬ 4 mM. At concentrations Ͼ 1 mM, 5 ␣ -cyprinol sulfate solubilized monooleylglycerol efficiently (2.1 molecules per mol micellar bile salt). When infused intravenously into the anesthetized rat, 5 ␣ -cyprinol sulfate was hemolytic, cholestatic, and toxic. In the isolated rat liver, it underwent little biotransformation and was poorly transported (T max Х 0.5 mol/min/kg) as compared with taurocholate. 5 ␣ -Cyprinol, its bile alcohol moiety, was oxidized to its corresponding C 27 bile acid and to allocholic acid (the latter was then conjugated with taurine); these metabolites were efficiently transported. 5 ␣ -Cyprinol sulfate inhibited taurocholate uptake in COS-7 cells transfected with rat asbt , the apical bile salt transporter of the ileal enterocyte. 5 ␣ -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 5 ␣ -cyprinol sulfate was present at micellar concentrations, and that it did not undergo hydrolysis during intestinal transit. These studies indicate that 5 ␣ -cyprinol sulfate is an excellent digestive detergent and suggest that a micellar phase is present during digestion in cyprinid fish. -Goto, T., F. Holzinger, L. R. Hagey, C. Cerrè, H-T. Ton-Nu, C. D. Schteingart, J. H. Steinbach, B. L. Shneider, and A. F. Hofmann. Physicochemical and physiological properties of 5 ␣ -cyprinol sulfate, the toxic bile salt of cyprinid fish.

Ligand specificity and evolution of liver X receptors

“…Other than those described above, steroids and bile salts were obtained from Steraloids (Newport, RI, USA). As previously described [12,13], 5α-cyprinol and 5α-cyprinol 27-sulfate were isolated from Asiatic carp (Cyprinus carpio) bile, 5β-scymnol and 5β-scymnol 27-sulfate were isolated from Spotted eagle ray (Aetobatus narinari) bile, and taurine-amidated 5β-cholestan-3α,7α,12α-triol-27-oic acid was isolated from the bile of the American alligator (Alligator mississippiensis). 5β-Cyprinol was generously provided by the laboratory of Dr. Alan F. Hofmann (University of California -San Diego, CA, United States).…”

Bile salts of vertebrates: structural variation and possible evolutionary significance

“…To what extent this occurs is not known. For 5 ␣ -cyprinol (3 ␣ ,7 ␣ ,12 ␣ ,26,27-pentahydroxy-5 ␣ -cholestane), the main bile alcohol of cypriniform fi sh, the liberated bile alcohol is unlikely to be absorbed from the intestine because of the large number of hydroxy groups as well as the limited solubility of the unsulfated bile alcohol ( 13 ). As a result, in these fi sh, biliary bile alcohols are entirely primary, and the same is likely to be true for other species in which bile alcohol sulfates are present.…”

Identification, release and olfactory detection of bile salts in the intestinal fluid of the Senegalese sole (Solea senegalensis)

“…Alternatively, the meaning of the chemical message may depend on context or ratio or timing. Nevertheless, taurocholic acid is not the only bile acid that sole can smell; they also have sensitivity to sulphated C 27 bile salts 5 -scymnol sulphate and 5 -cyprinol sulphate (Velez et al 2007a) produced by other Wsh species (Haslewood 1967;Goto et al 2003). Thus, olfactory sensitivity to bile acids is not conWned to those produced by conspeciWcs.…”