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    
Abstract/OtherAbstract:
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.
Authors:
M A Tirmenstein; S D Nelson
Related Documents :
12557246 - Antioxidant effect of polyamines on erythrocyte cell membrane lipoperoxidation after fr...
3564056 - In vivo and in vitro hepatotoxicity and metabolism of acetaminophen in syrian hamsters.
24183066 - Applicability of the linear-quadratic formalism for modeling local tumor control probab...
24119416 - Dosimetric errors during treatment of centrally located lung tumors with stereotactic b...
7014476 - Induction of igm immunological memory to lipoteichoic acids in rabbits. part i.
9291356 - Enhancement of murine intestinal stem cell survival after irradiation by keratinocyte g...
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    
Affiliation:
Department of Medicinal Chemistry, University of Washington, Seattle 98195.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acetaminophen / 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:
DK 30699/DK/NIDDK NIH HHS; GM 25418/GM/NIGMS NIH HHS
Chemical
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 3.6.1.8/Calcium-Transporting ATPases

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


Previous Document:  Occurrence in vivo of selenocysteyl-tRNA(SERUCA) in Escherichia coli. Effect of sel mutations.
Next Document:  Different receptor subtypes mediate the dual presynaptic effects of 5-hydroxytryptamine on periphera...