TY - JOUR
T1 - A Nonhuman Primate Model of Gilbert's Syndrome
AU - Portman, Oscar W.
AU - Chowdhury, Jayanta Roy
AU - Chowdhury, Namita Roy
AU - Alexander, Manfred
AU - Cornelius, Charles E.
AU - Arias, Irwin M.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1984
Y1 - 1984
N2 - 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 [3H]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.
AB - 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 [3H]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.
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U2 - 10.1002/hep.1840040202
DO - 10.1002/hep.1840040202
M3 - Article
C2 - 6706295
AN - SCOPUS:0021240156
SN - 0270-9139
VL - 4
SP - 175
EP - 179
JO - Hepatology
JF - Hepatology
IS - 2
ER -