A nonhuman primate model of Gilbert's syndrome.
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 microM; mean +/- S.E.) and postcibal (9.9 +/- 0.9 microM) plasma unconjugated bilirubin concentrations (p less than 0.001) than a closely related Brazilian population (fasting 5.5 +/- 0.7 microM); postcibal (2.4 +/- 0.7 microM). After intravenous administration of [3H]bilirubin as a tracer dose or at 3.4 mumoles 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 less than 0.01 and 4.1 +/- 0.1--p less than 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 microM) and postcibal (5.3 +/- 1 microM) plasma bilirubin concentrations in Bolivian monkeys were significantly reduced (p less than 0.001). Sulfobromophthalein clearance was slightly slower in the Bolivian than in the Brazilian monkeys. SGOT, lactate dehydrogenase, gamma-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 less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001663:Bilirubin / Q000097:blood*; D002427:Cebidae / Q000097:blood*; D004195:Disease Models, Animal; D004905:Erythrocyte Aging; D005878:Gilbert Disease / Q000097:blood* / Q000473:pathology; D006933:Hyperbilirubinemia, Hereditary / Q000097:blood*; D008099:Liver / Q000473:pathology*; D008111:Liver Function Tests; D010634:Phenobarbital / Q000494:pharmacology; D012453:Saimiri / Q000097:blood*; D013448:Sulfobromophthalein
D013448:Sulfobromophthalein; D001663:Bilirubin; D010634:Phenobarbital