Heterogeneous distribution of drug metabolism in elutriated rat hepatocytes |
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| Authors: | R A Willson H H Liem K Miyai U Muller-Eberhard |
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| Affiliation: | 1. Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), Islamabad, Pakistan;2. Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan, India;3. Department of Botany, S.P. College, Srinagar, Jammu and Kashmir, India;1. Clean Combustion Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia;2. Mechanical Engineering Program, Physical Science and Engineering Division, King Abdullah University of Science and Technology, Saudi Arabia;3. Purdue University, West Lafayette, IN, United States;1. Office of Testing and Research, Center of Drug Evaluation and Research, US Food and Drug Administration, Saint Louis, MO 63110, USA;2. TGA Laboratories, 136 Narrabundah Lane, Symonston, Canberra, A.C.T 2606, Australia;3. Health Products Laboratory Program, Regulatory Operations and Enforcement Branch, Department of Health, Government of Canada, 2301 Midland Ave, Toronto ON, M1P 4R7, Canada;4. French National Agency for the Safety of Medicines and Health Products (ANSM), Laboratory Controls Division; 635 Rue de la Garenne, 34740 Vendargues, France;5. Department of Pharmacy (OMCL), Bavarian Health and Food Safety Authority, Veterinaerstr. 2 85764 Oberschleissheim, Germany;6. Schweizerisches Heilmittelinstitut (Biol. & Pharm.), OMCL Swissmedic, Hallerstrasse 7, 3012, Bern, Switzerland;7. Biological Standardisation, OMCL Network & HealthCare Department (DBO), EDQM – Council of Europe – Conseil de l''Europe, 7 Allée Kastner CS 30026 F- 67081 Strasbourg, France |
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| Abstract: | Centrifugal elutriation was used to separate isolated rat hepatocytes into five fractions containing cells of different sizes. These fractions were compared with regard to cell size, morphology and function. Analyzed by flow cytometry, the small cells were found to be enriched in fraction 1 and the large cells in fraction 5. Evaluation by light and electron microscopy indicated that the fractions contained single hepatocytes of normal structure. The cytochrome P-450 content and the 7-ethoxycoumarin O-deethylase activity were assessed in hepatocytes from untreated animals, those treated with phenobarbital, and those treated with phenobarbital plus allylisopropylacetamide. In both untreated and phenobarbital-treated animals, cytochrome P-450 content and 7-ethoxycoumarin O-deethylase activity rose significantly from fraction 1 to fraction 5. The P-450 content gradually rose up to 2-fold. The enzyme activity rose 5-fold, and it increased steeply between fractions 2 and 3. The cytochrome P-450 content in phenobarbital-plus-allylisopropylacetamide-treated animals was decreased in all fractions but more extensively in fraction 5 than in fraction 1. |
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