Resistance of the Suckling Guinea Pig to Lithocholic Acid-Induced Cholestasis

Authors

  • Malka Lewittes,

    1. Departments of Pediatrics, Nutrition and Pharmacology, University of Montreal, and Centre de Recherche Pediatrique, Hopital Sainte-Justine, Montreal, Quebec, Canada H3T1C5
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  • Beatrix Tuchweber,

    1. Departments of Pediatrics, Nutrition and Pharmacology, University of Montreal, and Centre de Recherche Pediatrique, Hopital Sainte-Justine, Montreal, Quebec, Canada H3T1C5
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  • Andree Weber,

    1. Departments of Pediatrics, Nutrition and Pharmacology, University of Montreal, and Centre de Recherche Pediatrique, Hopital Sainte-Justine, Montreal, Quebec, Canada H3T1C5
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  • Claude C. Roy,

    1. Departments of Pediatrics, Nutrition and Pharmacology, University of Montreal, and Centre de Recherche Pediatrique, Hopital Sainte-Justine, Montreal, Quebec, Canada H3T1C5
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  • Ibrahim M. Yousef

    Corresponding author
    1. Departments of Pediatrics, Nutrition and Pharmacology, University of Montreal, and Centre de Recherche Pediatrique, Hopital Sainte-Justine, Montreal, Quebec, Canada H3T1C5
    • Ibrahim M. Yousef, Ph.D., Centre de Recherche Pediatrique, Hopital Sainte-Justine, 3175 Cote Sainte-Cath-erine, Montreal, Quebec, Canada H3T 1C5
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  • This study was also performed in part by Miss Lewittes during her M.S. research program in the Department of Pharmacology

Abstract

Although immaturity of the liver and synthesis of monohydroxy bile acids have been implicated as pathogenic factors in neonatal cholestasis, there is no direct evidence to show that these bile acids induce cholestasis in the newborn. In the present investigation, we compared the effects of lithocholic acid (LCA) injection on bile flow in suckling (2-week-old) and adult (12-week-old) guinea pigs. Bile flow was not modified by LCA in 2-week-old animals, but it was reduced by 50 to 80% in the adults, the decrease being dose-dependent. In the newborn, the injected LCA was mainly secreted in bile (>90%), while in the adults it was distributed between the liver and bile. The percentage of biliary bile acids (as determined by gas-liquid chromatography) in the two groups was similar before and after LCA injection. Morphologic lesions characteristic of LCA-induced cholestasis were observed only in the adult guinea pigs. This study demonstrates that the newborn guinea pig is less susceptible to cholestasis induced by 90 to 180 /imoles per kg body weight of lithocholate and that, in the neonatal liver, there is no defect in the transport of this bile acid from blood to bile.

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