The role of calcium precipitation in the sulfoglycolithocholate-induced cholestasis of the bile fistula hamster.
Sulfate glycolithocholic acid (SGLC) has been shown to be highly cholestatic in the rat. This study was performed in order to gain understanding of the mechanisms of SGLC-induced cholestasis and the aim of the investigation was to explore the hypothesis that SGLC could cause a precipitation of calcium in bile. We studied the effects of intravenously administrated SGLC on bile flow, biliary lipids secretion and calcium excretion in the female bile fistula hamster. We also performed in-vitro studies with a Ca2(+)-selective electrode in order to measure the calcium binding capacity of SGLC. The results showed that after 1 h of infusion of 8 mumol/100 g body weight [14C]SGLC bile flow dropped to zero. During the infusion period a fine white sludge was visible in the test tube used for bile collection. TLC and HPLC analysis of both the supernatant and the precipitate showed that unchanged SGLC was excreted into bile. Up to 20% of biliary SGLC and more than 50% of the total Ca2+ present in bile was precipitated. The SGLC/Ca2+ molar ratio in the precipitate was 1.12 +/- 0.3 (mean +/- S.D. of four experiments). Light and electron microscopy of the liver did not show any specific abnormalities. The Ca2+ binding activity of SGLC in vitro, was highest among the bile acids tested at a concentration of 0.1 mM, when almost 100% of bile acids are in the monomeric (non-micellar) form. This suggests that among the bile acids, SGLC exerts the strongest binding activity on free calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS)
Bellentani
S
S
Fondo per lo Studio delle Malattie del Fegato, Italy.
Armocida
C
C
Pecorari
M
M
Saccoccio
G
G
Marchegiano
P
P
Angeloni
A
A
Manenti
F
F
Ricci
G L
GL
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism; D001658:Biliary Fistula / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002779:Cholestasis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D004566:Electrodes; D005260:Female; D006000:Glycocholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007262:Infusions, Intravenous; D050356:Lipid Metabolism; D008647:Mesocricetus
D001647:Bile Acids and Salts; C018154:sulfolithocholylglycine; D006000:Glycocholic Acid; D002118:Calcium