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Lithocholate-3-O-glucuronide-induced cholestasis

A study with congenital hyperbilirubinemic rats and effects of ursodeoxycholate conjugates

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Abstract

The mechanism of lithocholate-3-O-glucuronide-induced cholestasis is unknown. In this study, we investigated the cholestatic effects of this agent in a congenital hyperbilirubinemic rat, EHBR. We also studied the effects of ursodeoxycholate-3-O-glucuronide and tauroursodeoxycholate on lithocholate-3-O-glucuronide-induced cholestasis in rats. Lithocholate-3-O-glucuronide, administered at the rate of 0.1 μmol/min/100 g for 40 min, a cholestatic dose in control rats, failed to cause cholestasis in EHBR, and biliary lithocholate-3-O-glucuronide excretion was delayed. Biliary concentrations of this agent did not correlate with the severity of cholestasis. Both tauroursodeoxycholate and ursodeoxycholate-3-O-glucuronide, infused at the rate of 0.2 μmol/min/100 g for 120 min, completely inhibited cholestasis induced by lithocholate-3-O-glucuronide administered at the rate of 0.1 μmol/min/100 g for 40 min. Only tauroursodeoxycholate enhanced biliary lithocholate-3-O-glucuronide excretion. These findings indicate that lithocholate-3-O-glucuronide-induced cholestasis is induced by damage at the level of the bile canalicular membrane. Ursodeoxycholate-3-O-glucuronide inhibits this cholestasis, possibly by inhibiting the access of lithocholate-3-O-glucuronide to the bile canalicular membrane.

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Authors and Affiliations

  1. Department of Medicine, Teikyo University School of Medicine, Kaga 2-11-1, 173, Itabashi-ku, Tokyo, Japan

    Hajime Takikawa MD, Kazutaka Minagawa MD, Naoyo Sano BS & Masami Yamanaka MD

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  1. Hajime Takikawa MD
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  2. Kazutaka Minagawa MD
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  3. Naoyo Sano BS
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  4. Masami Yamanaka MD
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Takikawa, H., Minagawa, K., Sano, N. et al. Lithocholate-3-O-glucuronide-induced cholestasis. Digest Dis Sci 38, 1543–1548 (1993). https://doi.org/10.1007/BF01308618

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  • DOI: https://doi.org/10.1007/BF01308618

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