| Toxicity of uricosuric diuretics in rat hepatocyte culture. | |
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MedLine Citation:
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PMID: 2706015 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several aryloxyacetic acid diuretics have shown hepatotoxicity in humans, yet there continues to be interest in developing these compounds because of the uricosuric properties of some of them. This study was designed to test the utility of the hepatocyte monolayer culture as a model for studying these compounds. In addition, an attempt was made to define the structural components that are common to hepatotoxicity. Ticrynafen, indacrinone, ethacrynic acid and A-49816, an investigational compound, were found to be toxic in hepatocyte cultures; thus, with the exception of indacrinone, paralleling the experience in humans. The toxic compounds share a ketodichlorophenoxyacetic acid chemical structure. A-56234, an investigational uricosuric, was also found to be toxic in cultures but has not been demonstrated to be hepatotoxic in humans in limited clinical experience. It does not possess the ketodichlorophenoxyacetic acid structure proper but may be metabolized to a closely related structure. Furosemide, which does not have the ketodichlorophenoxyacetic acid structure, was not toxic in hepatocyte cultures and has not been hepatotoxic in humans. Thus, the structure common to the toxic compounds is ketodichlorophenoxyacetic acid or a closely related compound. The hepatocyte monolayer system appears to be a good model for demonstrating toxicity and, perhaps, for predicting toxicity of new compounds under development. |
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Authors:
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K G Tolman; P D Gray; S el Masry; R R Luther; R S Janicki |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochemical pharmacology Volume: 38 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1989 Apr |
Date Detail:
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Created Date: 1989-05-12 Completed Date: 1989-05-12 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1181-4 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Diuretics / toxicity* Drug Evaluation, Preclinical / methods Ethacrynic Acid / toxicity Glycolates / toxicity Indans / toxicity Liver / drug effects* Male Models, Biological Rats Rats, Inbred Strains Ticrynafen / toxicity Uricosuric Agents / toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Diuretics; 0/Glycolates; 0/Indans; 0/Uricosuric Agents; 40180-04-9/Ticrynafen; 56049-88-8/indanone; 58-54-8/Ethacrynic Acid; 78235-72-0/A 49816 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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