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  • Title: Sex differences of nicotinate-induced hyperbilirubinemia in Gilbert's syndrome. Implication of bilitranslocase function.
    Author: Gentile S, Tiribelli C, Baldini G, Lunazzi G, Sottocasa GL.
    Journal: J Hepatol; 1985; 1(4):417-29. PubMed ID: 3840503.
    Abstract:
    Intravenous administration of nicotinic acid (NA) is followed by an increase in serum unconjugated bilirubin level. This effect is higher in Gilbert's syndrome (GS) and this test has been used in the diagnosis of the syndrome. After administration of 5.9 mumol NA/kg body weight, the maximal increment of serum unconjugated bilirubin and the area under the bilirubin concentration time curve (AUC) were significantly higher (P less than 0.01) in GS males than in GS females. The half-life of the first fast slope of plasma disappearance curve of the drug was also significantly prolonged in GS males as compared to GS females (15.91 +/- 1.12 vs 9.13 +/- 1.25 min, mean +/- SEM, P less than 0.005). The maximal bilirubin increment and AUC were linearly correlated (P less than 0.01) with NA plasma half-life. Purified preparations of bilitranslocase, a liver plasma-membrane protein involved in bilirubin and sulfobromophthalein (BSP) transport, specifically bound NA and the drug competitively inhibited BSP uptake in rat liver plasma membrane vesicles (Ki = 50 nM). These data suggest that, in addition to the hemolytic effect of the drug, NA-induced hyperbilirubinaemia could be also due to a competition between the two anions at the sinusoidal plasma membrane level. A possible implication of bilitranslocase in GS is considered.
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