| Naproxen-induced oxidative stress in the isolated perfused rat liver. | |
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MedLine Citation:
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PMID: 16472794 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We previously showed that naproxen induced the oxidative stress in the liver microsomes and the isolated hepatocytes of rats. In this study, the in situ effect of naproxen on the rat liver tissue was investigated, using the isolated perfused liver from the view-point of the naproxen-induced hepatotoxicity. The leakage of glutamic-oxaloacetic transaminase (GOT) from the perfused liver and appearance of thiobarbituric acid reactive substances (TBARS) in the perfusate increased with the progress of perfusion after a lag time of about 1h. The naproxen-perfusion of the liver decreased the biliary excretion of glutathione (GSH) and oxidized glutathione, glutathione disulfide (GSSG) prior to TBARS production and GOT leakage. GSSG content in the naproxen-perfused liver was significantly higher than in the control. TBARS appeared in the perfusate of the naproxen-perfused liver for 30 min, but not in the control. The biliary excretion clearance (CL(bile)) of indocyanine green (ICG), a reagent for testing the liver function, in the liver perfused with naproxen decreased to a half of that in the liver perfused without naproxen. Thus, the naproxen-induced oxidative stress in the liver was shown to affect the physiological function of liver through the impairment of biliary excretion, which is recognized as a detoxification system. |
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Authors:
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Hiroyuki Yokoyama; Toshiharu Horie; Shoji Awazu |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2006-02-10 |
Journal Detail:
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Title: Chemico-biological interactions Volume: 160 ISSN: 0009-2797 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 2006 Mar |
Date Detail:
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Created Date: 2006-03-10 Completed Date: 2006-04-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: Ireland |
Other Details:
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Languages: eng Pagination: 150-8 Citation Subset: IM |
Affiliation:
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Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents, Non-Steroidal / toxicity* Aspartate Aminotransferases / metabolism Bile / secretion Dose-Response Relationship, Drug Glutathione / metabolism Glutathione Disulfide / metabolism Liver / drug effects*, metabolism Liver Function Tests Male Naproxen / toxicity* Oxidative Stress / drug effects* Perfusion Rats Rats, Wistar Thiobarbituric Acid Reactive Substances / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Thiobarbituric Acid Reactive Substances; 22204-53-1/Naproxen; 27025-41-8/Glutathione Disulfide; 70-18-8/Glutathione; EC 2.6.1.1/Aspartate Aminotransferases |
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