Cholestasis induced by lithocholate and its glucuronide: their biliary excretion and metabolism.
We studied the effects of the infusion of lithocholate and lithocholate-3-sulfate and 3-glucuronide in rats (0.29 mumol/min per 100 g body weight for 40 min) on bile flow, together with their biliary excretion and metabolism. Lithocholate-glucuronide had a higher cholestatic effect than lithocholate, whereas lithocholate-sulfate had almost no effect on bile flow. Lithocholate was mainly converted to taurine or glucuronide conjugates in the bile, serum and liver and hydroxylation of the tauro-conjugate proceeded. Lithocholate-sulfate was almost completely excreted in the bile, mainly as tauro-conjugate. Lithocholate-glucuronide was excreted in bile almost without conjugation, while some taurine conjugation occurred in the serum and liver. These results suggest that the poor biotransformation of lithocholate-glucuronide is related to its higher cholestatic potency than lithocholate.
Takikawa
H
H
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Ohki
H
H
Sano
N
N
Kasama
T
T
Yamanaka
M
M
D000410:Alanine Transaminase / Q000096:biosynthesis; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000097:blood / Q000302:isolation & purification; D001663:Bilirubin / Q000097:blood; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D005965:Glucuronates / Q000378:metabolism; D007700:Kinetics; D008095:Lithocholic Acid / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016339:Spectrometry, Mass, Fast Atom Bombardment
D001647:Bile Acids and Salts; D005965:Glucuronates; D008095:Lithocholic Acid; C041558:lithocholate 3-O-glucuronide; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin