| Subcellular binding and effects on calcium homeostasis produced by acetaminophen and a nonhepatotoxic regioisomer, 3'-hydroxyacetanilide, in mouse liver. | |
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MedLine Citation:
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PMID: 2524496 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Acetaminophen (250 mg/kg) administered intraperitoneally to fasted, phenobarbital-induced mice produced hepatotoxicity. No hepatotoxicity was observed after the administration of the regioisomer 3'-hydroxyacetanilide (600 mg/kg). Similar levels of covalent binding to liver homogenates occurred in mice receiving either acetaminophen or 3'-hydroxyacetanilide at these doses. However, subcellular fractionation techniques revealed that the acetaminophen treatment produced greater levels of covalent binding to mitochondrial proteins than 3'-hydroxyacetanilide. In addition, acetaminophen depleted mitochondrial glutathione levels more extensively than 3'-hydroxyacetanilide. Plasma membrane calcium-ATPase activity was reduced to 79.8% and 55.7% of control values at 1 h and 6 h, respectively, following the administration of acetaminophen. No inhibition of this enzyme was detected in mice receiving 3'-hydroxyacetanilide. Acetaminophen also induced alterations in mitochondrial calcium levels and decreased the ability of isolated mitochondria to sequester calcium. These effects were not produced by 3'-hydroxyacetanilide. Our results indicate that acetaminophen induces alterations in calcium homeostasis while 3'-hydroxyacetanilide does not. |
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Authors:
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M A Tirmenstein; S D Nelson |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 264 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1989 Jun |
Date Detail:
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Created Date: 1989-07-13 Completed Date: 1989-07-13 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 9814-9 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, University of Washington, Seattle 98195. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetaminophen
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pharmacology* Acetanilides / pharmacology* Analgesics / pharmacology* Animals Calcium / metabolism* Calcium-Transporting ATPases / metabolism Cell Membrane / enzymology Glutathione / analogs & derivatives, metabolism Glutathione Disulfide Homeostasis / drug effects Isomerism Kinetics Liver / drug effects, metabolism* Male Mice Mitochondria, Liver / drug effects, metabolism* Reference Values Subcellular Fractions / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK 30699/DK/NIDDK NIH HHS; GM 25418/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acetanilides; 0/Analgesics; 103-90-2/Acetaminophen; 27025-41-8/Glutathione Disulfide; 621-42-1/3-hydroxyacetanilide; 70-18-8/Glutathione; 7440-70-2/Calcium; EC 3.6.1.8/Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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