Document Detail

Subcellular binding and effects on calcium homeostasis produced by acetaminophen and a nonhepatotoxic regioisomer, 3'-hydroxyacetanilide, in mouse liver.
MedLine Citation:
PMID:  2524496     Owner:  NLM     Status:  MEDLINE    
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.
M A Tirmenstein; S D Nelson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  264     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1989 Jun 
Date Detail:
Created Date:  1989-07-13     Completed Date:  1989-07-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9814-9     Citation Subset:  IM    
Department of Medicinal Chemistry, University of Washington, Seattle 98195.
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MeSH Terms
Acetaminophen / pharmacology*
Acetanilides / pharmacology*
Analgesics / pharmacology*
Calcium / metabolism*
Calcium-Transporting ATPases / metabolism
Cell Membrane / enzymology
Glutathione / analogs & derivatives,  metabolism
Glutathione Disulfide
Homeostasis / drug effects
Liver / drug effects,  metabolism*
Mitochondria, Liver / drug effects,  metabolism*
Reference Values
Subcellular Fractions / metabolism
Grant Support
Reg. No./Substance:
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 ATPases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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