Temporal aspects of carbon tetrachloride-induced alteration of sulfobromophthalein excretion and metabolism |
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| Authors: | B G Priestly G L Plaa |
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| Affiliation: | 1. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;2. Institute of Cancer Sciences, The University of Glasgow, Glasgow, United Kingdom;3. Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom;1. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK;2. Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK;1. Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang #24, Nanjing, Jiangsu 210009, China;2. Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang #24, Nanjing, Jiangsu 210009, China;3. National Drug Clinical trial Institute, The Second Affiliated Hospital, Xi''an Jiaotong University, Xi''an, Shaanxi 710004, China;4. Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210009, China |
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| Abstract: | Impairment of hepatic excretory function and hepatic conjugation of sulfobromophthalein (BSP) conjugation both contribute to BSP plasma retention in rats 24 hr after oral administration of carbon tetrachloride (CCl4). The present study attempts to define the role of each of these parameters on the onset of plasma BSP retention. Impaired BSP excretion, bile flow rate, relative hepatic storage, and plasma BSP retention were observed as early as 3 hr after CCl4 administration. However, impaired BSP conjugation was not unequivocally demonstrated until 12 hr after CCl4. In experiments where BSP was administered by slow iv infusion (2.5 mg/min/kg), increases in the ratio of biliary unconjugated BSP to conjugated BSP were suggestive of impaired conjugation during the early stages of intoxication, although such changes were not marked when BSP was rapidly injected (60 mg/kg, iv). It is concluded that impaired hepatic excretory function is the prime factor involved in the onset of BSP retention after CCl4. |
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