Hepatotoxic bile acids increase cytosolic Ca++ activity of isolated rat hepatocytes

Hepatology. Jul-Aug 1988;8(4):887-91. doi: 10.1002/hep.1840080430.

Abstract

Effects of bile acids on cystolic Ca++ activity and cell viability of isolated rat hepatocytes were studied to test the hypothesis that bile acids may produce hepatotoxicity by increasing cystolic Ca++ activity. Changes in cystolic Ca++ activity were calculated from time-dependent changes in fluorescence of quin-2 loaded hepatocytes. Release of lactate dehydrogenase and changes in propodium iodide fluorescence were used to assess cell viability. Bile acids studied were unconjugated and taurine-conjugated cholate, chenodeoxycholate (and taurochenodeoxycholate), deoxycholate (and taurodeoxycholate) and lithocholate (and taurolithocholate). With the exception of cholate and taurocholate, bile acids increased cystolic Ca++ activity within 10 to 30 sec in a concentration-dependent fashion (0.05 to 1.0 mM) and in the order lithocholate = taurolithocholate greater than chenodeoxycholate = taurochenodeoxycholate = deoxycholate = taurodeoxycholate. The initial increase in cystolic Ca++ activity by bile acids was not due to cell damage, since bile acid-induced decreases in cell viability were not significant until 2 to 3 min. At higher concentrations of unconjugated bile acid, there was a secondary increase in quin-2 fluorescence corresponding temporally to the increase in propodium iodide fluorescence, indicating cell damage after the initial increase in cystolic Ca++ activity. The ability of conjugated and unconjugated bile acids to increase cystolic Ca++ activity was abolished and decreased (60 to 90%), respectively, in the absence of extracellular Ca++, indicating that extracellular Ca++ is the major source of the bile acid-induced increase in cystolic Ca++ activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

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

MeSH terms

  • Animals
  • Bile Acids and Salts / pharmacology*
  • Bile Acids and Salts / toxicity
  • Calcium / metabolism*
  • Cell Membrane Permeability
  • Cell Survival / drug effects
  • Cytosol / metabolism
  • In Vitro Techniques
  • L-Lactate Dehydrogenase / metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Rats
  • Rats, Inbred Strains

Substances

  • Bile Acids and Salts
  • L-Lactate Dehydrogenase
  • Calcium