Hepatotoxicity after 3'-hydroxyacetanilide administration to buthionine sulfoximine-pretreated mice

The administration of 3'-hydroxyacetanilide, a regioisomer of acetaminophen, to mice failed to produce hepatotoxicity even after the administration of diethyl maleate. In contrast, hepatotoxicity did occur when 3'-hydroxyacetanilide was administered to buthionine sulfoximine pretreated mic...

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Bibliographic Details
Published in:Chemical research in toxicology 1991-03, Vol.4 (2), p.214-217
Main Authors: Tirmenstein, Mark A, Nelson, Sidney D
Format: Article
Language:English
Subjects:
Acetaminophen - adverse effects
Acetaminophen - metabolism
Alanine Transaminase - blood
Animals
Antimetabolites, Antineoplastic - pharmacology
Biological and medical sciences
Buthionine Sulfoximine
Drug Interactions
Drug toxicity and drugs side effects treatment
Glutathione - metabolism
Liver - drug effects
Liver - metabolism
Male
Maleates - pharmacology
Medical sciences
Methionine Sulfoximine - analogs & derivatives
Methionine Sulfoximine - pharmacology
Mice
Mitochondria, Liver - metabolism
Pharmacology. Drug treatments
Time Factors
Toxicity: digestive system
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Summary:The administration of 3'-hydroxyacetanilide, a regioisomer of acetaminophen, to mice failed to produce hepatotoxicity even after the administration of diethyl maleate. In contrast, hepatotoxicity did occur when 3'-hydroxyacetanilide was administered to buthionine sulfoximine pretreated mice. Although the administration of 3'-hydroxyacetanilide in conjunction with either diethyl maleate or buthionine sulfoximine depleted total hepatic glutathione, only the combined buthionine sulfoximine-3'-hydroxyacetanilide treatment decreased hepatic mitochondrial glutathione concentrations to below 20% of control values. In addition, pretreatment with buthionine sulfoximine increased the amount of 3'-hydroxyacetanilide bound to mitochondrial proteins. These results, in conjunction without previous results on the involvement of mitochondrial damage in the pathogenesis of hepatotoxicity caused by acetaminophen, suggest a probable relationship between mitochondrial damage caused by the buthionine sulfoximine-3'-hydroxyacetanilide treatment and hepatotoxicity caused by this treatment.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx00020a014