Cholestasis induced by sulphated glycolithocholic acid in the rat: protection by endogenous bile acids
| Autor: | Roel J. Vonk, Folkert Kuipers, Rick Havinga |
|---|---|
| Rok vydání: | 1985 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Phospholipid Endogeny Bile Acids and Salts chemistry.chemical_compound Pharmacokinetics Cholestasis Internal medicine medicine Potency Animals Bile Bile acid Chemistry Cholesterol Rats Inbred Strains General Medicine medicine.disease Glycolithocholic acid Rats Kinetics Endocrinology Secretory Rate Glycocholic Acid |
| Zdroj: | Clinical science (London, England : 1979). 68(2) |
| ISSN: | 0143-5221 |
| Popis: | 1. Sulphated glycolithocholic acid (SGLC) causes cholestasis in experimental animals, despite its sulphated form. In the present study, the cholestatic potency and the pharmacokinetics of SGLC were investigated in rats under two conditions: (a) in the presence of an intact circulating bile acid pool and (b) after exhaustion of the bile acid pool by 24 h of bile diversion. 2. Intravenous administration of SGLC (8 μmol/ 100 g body weight) to rats with an intact bile acid pool did not cause cholestasis. However, biliary phospholipid and cholesterol concentrations were reduced by 40% and 29% respectively during the first hour after administration. When the same dose of the bile acid was injected in rats with a 24 h biliary drainage, a complete cessation of bile production was observed within 1 h. Twelve hours after the onset of cholestasis, bile production gradually increased again, showed a marked overshoot, and reached control levels after 3 days. In the recovery phase, biliary phospholipid and cholesterol concentrations were greatly reduced. 3. The absence of endogenous bile acids did not change the hepatic clearance rate of a tracer dose of radiolabelled SGLC, but markedly decreased its biliary excretion rate. 4. It was concluded that the hepatotoxic effect of SGLC is much more pronounced in rats with an exhausted bile acid pool, possibly due to a slower biliary excretion of the toxic compound. This phenomenon may have clinical implications for patients with a contracted bile acid pool. |
| Databáze: | OpenAIRE |
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