Hepatotoxicological evaluation of dantrolene sodium

J. A. Durham, A Jay Gandolfi, J. B. Bentley

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The clinical use of dantrolene has been associated with hepatotoxicity, thus the toxicity of dantrolene in Swiss-Webster mice was characterized. Animals were treated orally (po) with single or multiple doses of up to 400 mg/kg of D without any increases in SGPT or alterations in hepato-cellular architecture. To possibly enhance the hepatotoxicity of dantrolene, its biotransformation was altered by inhibiting acetylation, depleting glutathione, inducing biotransformation, and promoting reductive metabolism. None of the metabolic alterations elicited any toxicity of dantrolene. Hepatic microsomal incubations were used to detect the possible bioactivation and covalent binding of 14C-dantrolene. Analysis for covalent adducts found only 20-30 pmol bound/mg microsomal protein. Thus the suspected hepatotoxicity of dantrolene does not appear to be linked to its biotransformation or bioactivation. Additional studies will be necessary to clarify if other parameters are necessary for dantrolene to be a hepatotoxin.

Original languageEnglish (US)
Pages (from-to)23-40
Number of pages18
JournalDrug and Chemical Toxicology
Volume7
Issue number1
DOIs
StatePublished - 1984

Fingerprint

Dantrolene
Sodium
Toxicity
Biotransformation
Acetylation
Metabolism
Animals
Proteins
Alanine Transaminase
Glutathione
Liver

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health
  • Chemical Health and Safety
  • Chemistry(all)

Cite this

Hepatotoxicological evaluation of dantrolene sodium. / Durham, J. A.; Gandolfi, A Jay; Bentley, J. B.

In: Drug and Chemical Toxicology, Vol. 7, No. 1, 1984, p. 23-40.

Research output: Contribution to journalArticle

Durham, J. A. ; Gandolfi, A Jay ; Bentley, J. B. / Hepatotoxicological evaluation of dantrolene sodium. In: Drug and Chemical Toxicology. 1984 ; Vol. 7, No. 1. pp. 23-40.
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