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A Nonhuman Primate Model of Gilbert's Syndrome
Author(s) -
Portman Oscar W.,
Chowdhury Jayanta Roy,
Chowdhury Namita Roy,
Alexander Manfred,
Cornelius Charles E.,
Arias Irwin M.
Publication year - 1984
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840040202
Subject(s) - bilirubin , medicine , endocrinology , phenobarbital , population , primate , saimiri sciureus , alkaline phosphatase , lactate dehydrogenase , glucuronosyltransferase , glutathione , biology , squirrel monkey , chemistry , microsome , biochemistry , enzyme , environmental health , neuroscience
A Bolivian population of squirrel monkeys, Saimiri sciureus , exhibits several features of Gilbert's syndrome in man, and is proposed as a nonhuman primate model of the condition. The Bolivian population was found to have higher fasting (40.6 ± 2.7 μM; mean ± S.E.) and postcibal (9.9 ± 0.9 μM) plasma unconjugated bilirubin concentrations (p < 0.001) than a closely related Brazilian population (fasting 5.5 ± 0.7 μM); postcibal (2.4 ± 0.7 μM). After intravenous administration of [ 3 H]bilirubin as a tracer dose or at 3.4 μmoles per kg body weight, there was delayed plasma clearance in the Bolivian monkeys. Hepatic UDP‐glucuronyl transferase activity for bilirubin (164 ± 25 nmoles per 30 min per gm liver) and biliary bilirubin diglucuronide to monoglucuronide ratios (2.9 ± 0.2) were lower in Bolivian monkeys than in Brazilians (421 ± 36 nmoles per 30 min per gm liver‐p < 0.01 and 4.1 ± 0.1–p < 0.02, respectively). Hepatic cytosol glutathione‐S‐transferase B activity (ligandin) levels were similar for the two populations. After phenobarbital therapy, fasting (11.1 ± 0.9 μM) and postcibal (5.3 ± 1 μM) plasma bilirubin concentrations in Bolivian monkeys were significantly reduced (p < 0.001). Sulfobromophthalein clearance was slightly slower in the Bolivian than in the Brazilian monkeys. SGOT, lactate dehydrogenase, ‐γ‐glutamyl transpeptidase and alkaline phosphatase activities were not increased in Bolivians. Fasting serum conjugated bile salt concentrations in Bolivian monkeys were lower than that in Brazilian monkeys (p < 0.01). Erythrocyte survival and hematological measurements were comparable in both populations.