Hepatic uptake and disposition of aflatoxin B1 in isolated perfused rat liver
| Autor: | Harihara M. Mehendale, A. Wallace Hayes, Peter D. Unger |
|---|---|
| Rok vydání: | 1977 |
| Předmět: |
Pharmacology
medicine.medical_specialty Aflatoxin Chemistry Metabolite bacterial infections and mycoses Toxicology Rats Perfusion Excretion chemistry.chemical_compound fluids and secretions Endocrinology Aflatoxins Liver Rat liver Internal medicine Total dose Acute exposure medicine Animals Bile Aflatoxin B |
| Zdroj: | Toxicology and Applied Pharmacology. 41:523-534 |
| ISSN: | 0041-008X |
| Popis: | Isolated perfused rat liver preparations were utilized to measure the hepatic uptake and biliary excretion of aflatoxin B 1 (AFB 1 ). Livers were perfused with 30% rat blood perfusate containing 6.4 μmol of AFB 1 and a series of timed blood and bile samples were extracted and analyzed by high-pressure liquid chromatography. Blood, bile, and liver samples also were radioassayed by liquid scintillation. Over 70% of AFB 1 was taken up by the liver from the recirculating perfusate within 5 min and less than 0.5% remained in the perfusate after 180 min of perfusion. AFB 1 was removed from the perfusate by a first-order process (monophasically) with a half-life of 18.6 ± 1.55 min (mean ± SE). By 4 hr of perfusion, 28.9% of the total AFB 1 -derived radioactivity was excreted into the bile. Less than 0.4% of the total dose of AFB 1 was excreted unchanged into the bile by 4 hr. The rates of biliary excretion of AFB 1 -derived radioactivity and parent compound reached a maximum at 30 min, after which time the rates of excretion decreased monophasically with half-lives of 47 ± 1.22 min (mean ± SE) for AFB 1 -derived radioactivity and 25.33 ± 1.08 min (mean ± SE) for the parent compound. One metabolite was detected in the perfusate plasma and at least five metabolites were seen in the bile. Bile flow was decreased after 90 min of perfusion and was completely stopped in two experiments by 120 min, and by the end of 240 min bile flow was stopped in all experiments. This observation indicates that AFB 1 is cholestatic upon acute exposure. |
| Databáze: | OpenAIRE |
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