Skip to main content
Log in

Effect of ethanol on the metabolism of lithocholic acid in rat liver

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Lithocholic acid 24-C14 is converted by 20000x g-supernatant of rat liver homogenate into several products of higher polarity. 3α-6β-dihydroxy-5β-cholanic acid is the main metabolite, whereas 7α-hydroxylation occurs only to a small extent. Besides of the hydroxylations conjugation with taurine and the formation of a 3-sulfate ester of lithocholic acid can be demonstrated. Addition of ethanol to the enzymatic system results in an inhibition of the formation of 3α,6β-dihydroxy-5β-cholanic acid, whereas no effect can be observed with respect to the formation of the other products. This inhibition is present also in 20000x g-supernatant obtained from rats pretreated with ethanol 100 min before being preparation from ethanol-pretreated rats amounts to 68% of the controls. The chrome P-450 mediated oxidative mechanism, which has been shown to be involved in microsomal 6β-hydroxylation of bile acids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Burstein, S., Jacobsohn, G. M., Lieberman, S.: The cleavage of androsterone-β-D-glucopyranosiduronic acid in organic media. J. Amer. chem. Soc. 82, 1226–1230 (1960).

    Google Scholar 

  • Burstein, S., Lieberman, S.: Kinetics and mechanism of solvolysis of steroid hydrogen sulfates. J. Amer. chem. Soc. 80, 5235–5239 (1958).

    Google Scholar 

  • Cronholm, T., Makino, I., Sjövall, J.: Steroid metabolism in rats given 1-2H2-ethanol. Oxidoreduction of isomeric 3-hydroxycholanoic acids and reduction of 3-oxo-4-cholenoic acid. Europ. J. Biochem. 26, 251–258 (1972).

    Google Scholar 

  • Danielsson, W., Einarsson, K.: In: The biological basis of medicine, Vol. 5, pp. 279–315. Edts. E. Bittar and N. Bittar. New York: Academic Press 1969.

    Google Scholar 

  • Einarsson, K., Johansson, G.: Effect of carbon monoxide and phenobarbital on hydroxylation of bile acids by rat liver microsomes. FEBS Letters 4, 177–180 (1969).

    Google Scholar 

  • Eneroth, P.: Thin-layer chromatography of bile acids. J. Lipid. Res. 4, 11–16 (1963).

    Google Scholar 

  • Holsti, D.: Cirrhosis of the liver induced in rabbits by gastric instillation of 3-monohydroxycholanic acid. Nature (Lond.) 186, 250 (1960).

    Google Scholar 

  • Johansson, G.: Effect of cholestyramine and diet on hydroxylations in the biosynthesis and metabolism of bile acids. Europ. J. Biochem. 17, 292–295 (1970).

    Google Scholar 

  • Laatikainen, T., Vihko, R.: Quantitation of C11O2 and C21O2 steroid mono- and disulfates in human bile. Steroids 14, 119–131 (1969).

    Google Scholar 

  • Makita, M., Wells, W. W.: Quantitative analysis of fecal bile acids by gas-liquid chromatography. Analyt. Biochem. 5, 523–530 (1963).

    Google Scholar 

  • Palmer, R. H.: Hemolytic effects of steroids. Nature (Lond.) 201, 1134–1135 (1964).

    Google Scholar 

  • Palmer, R. H.: Gallstones produced experimentally by lithocholic acid in rats. Science 148, 1339–1340 (1965).

    Google Scholar 

  • Palmer, R. H.: Toxic effects of lithocholic acid and related 5β-H-steroids. In: Bile salt metabolism, pp. 184–201. Edts. L. Schiff, J. B. Carey, Jr., and J. D. Dietschy. Springfield, Ill.: Ch. C. Thomas 1969.

    Google Scholar 

  • Palmer, R. H.: Bile acid sulfates: II. Formation, metabolism, and excretion of lithocholic acid sulfates in the rat. J. Lipid. Res. 12, 680–687 (1971).

    Google Scholar 

  • Palmer, R. H., Glickman, P. B., Kappas, A.: Pyrogenic and inflammatory properties of certain bile acids in man. J. clin. Invest. 41, 1573–1577 (1962).

    Google Scholar 

  • Rubin, E., Gang, H., Misra, P., Lieber, C. S.: Inhibition of drug metabolism by acute alcohol intoxication: a hepatic microsomal mechanism. Amer. J. Med. 49, 801–806 (1970).

    Google Scholar 

  • Rubin, E., Lieber, C. S., Alvares, A. P., Levin, W., Kuntzman, R.: Ethanol binding to hepatic microsomes. Its increase by ethanol consumption. Biochem. Pharmacol. 20, 229–231 (1971).

    Google Scholar 

  • Rubin, E., Lieber, C. S.: Hepatic microsomal enzymes in man and rat: Induction and inhibition by ethanol. Science 162, 690–691 (1968).

    Google Scholar 

  • Schlenk, H., Gellermann, J. L.: Esterification of fatty acids with diazomethane on a small scale. Analyt. Chem. 32, 1412–1414 (1960).

    Google Scholar 

  • Schüppel, R.: Hemmung der Hydroxylierung von Arzneimitteln in vivo unter Äthanolbelastung. Naunyn-Schmiedebergs Arch. Pharmak. 265, 156–169 (1969).

    Google Scholar 

  • Schüppel, R.: Wirkungen von Alkohol auf den Arzneistoffwechsel. In: Alcohol and the liver, pp. 228–239. Edts. W. Gerok, K. Sickinger, and H. H. Hennekeuser. Stuttgart-New York: F. K. Schattauer 1971.

    Google Scholar 

  • Sjövall, J., Eneroth, P., Ryhage, R.: Mass spectra of bile acids. In: The bile acids. Chemistry, physiology, and metabolism. Vol. 1, pp. 209–246. Edts. P. P. Nair and D. Kritchevsky. New York-London: Plenum Press 1971.

    Google Scholar 

  • Thomas, P. J., Hsia, S. L., Matchiner, J. T., Doisy, E. A., Jr., Elliot, W. E., Thayer, S., Doisy, E. A.: Bile acids XIX. Metabolism of lithocholic acid-24-14C in the rat. J. biol. Chem. 239, 102–105 (1964).

    Google Scholar 

  • Thurman, R. G., Ley, H. G., Scholz, R.: Hepatic microsomal ethanol oxidation. Hydrogen peroxide formation and the role of catalase. Europ. J. Biochem. 25, 420–430 (1972).

    Google Scholar 

  • Voigt, W., Hsia, S. L., Cooper, D. Y., Rosenthal, O.: Photoreactivation spectrum of the CO-inhibited taurochenodeoxycholate 6β-hydroxylase system. FEBS Letters 2, 124–126 (1968).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by the Deutsche Forschungsgemeinschaft.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Back, P., Schernau-Potzi, L. Effect of ethanol on the metabolism of lithocholic acid in rat liver. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 135–145 (1972). https://doi.org/10.1007/BF00508902

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00508902

Key words

Navigation