Bioactivation and hepatotoxicity of 2H/3H halothane

I. G. Sipes, A Jay Gandolfi

Research output: Contribution to journalArticle

Abstract

Results in rats suggest that scission of the C-H bond is not a determining factor in the hepatotoxicity of halothane, since no apparent differences in liver injury were observed between halothane and d-halothane. Also, no significant changes between halothane and d-halothane were found in the levels of those metabolites produced during the reductive biotransformation of halothane (F- and the volatile metabolites, CDE and CTE). However, deuterium substitution markedly reduced the oxidative biotransformation of halothane, as evidenced by the 60% decrease in debromination. The covalent binding data also indicate that scission of the C-H bond does not occur during reductive bioactivation of halothane, since the 3H was retained under reductive conditions. The differences in stoichiometry of the binding of 3H-halothane and 14C-halothane are interesting and may indicate that different reactive intermediates exist for binding to lipid or protein and/or for O2 or N2 atmospheres, or reflect isotope effects or isotope exchange reactions. However, binding of 3H-halothane equivalents may be a useful marker for reductive biotransformation of halothane and its associated toxicity.

Original languageEnglish (US)
JournalAnesthesiology
Volume51
Issue number3 SUPPL
StatePublished - 1979

Fingerprint

Halothane
Biotransformation
Isotopes
Deuterium
Atmosphere
Lipids

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Bioactivation and hepatotoxicity of 2H/3H halothane. / Sipes, I. G.; Gandolfi, A Jay.

In: Anesthesiology, Vol. 51, No. 3 SUPPL, 1979.

Research output: Contribution to journalArticle

@article{b948fdd872b74874b60abfe755d758f1,
title = "Bioactivation and hepatotoxicity of 2H/3H halothane",
abstract = "Results in rats suggest that scission of the C-H bond is not a determining factor in the hepatotoxicity of halothane, since no apparent differences in liver injury were observed between halothane and d-halothane. Also, no significant changes between halothane and d-halothane were found in the levels of those metabolites produced during the reductive biotransformation of halothane (F- and the volatile metabolites, CDE and CTE). However, deuterium substitution markedly reduced the oxidative biotransformation of halothane, as evidenced by the 60{\%} decrease in debromination. The covalent binding data also indicate that scission of the C-H bond does not occur during reductive bioactivation of halothane, since the 3H was retained under reductive conditions. The differences in stoichiometry of the binding of 3H-halothane and 14C-halothane are interesting and may indicate that different reactive intermediates exist for binding to lipid or protein and/or for O2 or N2 atmospheres, or reflect isotope effects or isotope exchange reactions. However, binding of 3H-halothane equivalents may be a useful marker for reductive biotransformation of halothane and its associated toxicity.",
author = "Sipes, {I. G.} and Gandolfi, {A Jay}",
year = "1979",
language = "English (US)",
volume = "51",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "3 SUPPL",

}

TY - JOUR

T1 - Bioactivation and hepatotoxicity of 2H/3H halothane

AU - Sipes, I. G.

AU - Gandolfi, A Jay

PY - 1979

Y1 - 1979

N2 - Results in rats suggest that scission of the C-H bond is not a determining factor in the hepatotoxicity of halothane, since no apparent differences in liver injury were observed between halothane and d-halothane. Also, no significant changes between halothane and d-halothane were found in the levels of those metabolites produced during the reductive biotransformation of halothane (F- and the volatile metabolites, CDE and CTE). However, deuterium substitution markedly reduced the oxidative biotransformation of halothane, as evidenced by the 60% decrease in debromination. The covalent binding data also indicate that scission of the C-H bond does not occur during reductive bioactivation of halothane, since the 3H was retained under reductive conditions. The differences in stoichiometry of the binding of 3H-halothane and 14C-halothane are interesting and may indicate that different reactive intermediates exist for binding to lipid or protein and/or for O2 or N2 atmospheres, or reflect isotope effects or isotope exchange reactions. However, binding of 3H-halothane equivalents may be a useful marker for reductive biotransformation of halothane and its associated toxicity.

AB - Results in rats suggest that scission of the C-H bond is not a determining factor in the hepatotoxicity of halothane, since no apparent differences in liver injury were observed between halothane and d-halothane. Also, no significant changes between halothane and d-halothane were found in the levels of those metabolites produced during the reductive biotransformation of halothane (F- and the volatile metabolites, CDE and CTE). However, deuterium substitution markedly reduced the oxidative biotransformation of halothane, as evidenced by the 60% decrease in debromination. The covalent binding data also indicate that scission of the C-H bond does not occur during reductive bioactivation of halothane, since the 3H was retained under reductive conditions. The differences in stoichiometry of the binding of 3H-halothane and 14C-halothane are interesting and may indicate that different reactive intermediates exist for binding to lipid or protein and/or for O2 or N2 atmospheres, or reflect isotope effects or isotope exchange reactions. However, binding of 3H-halothane equivalents may be a useful marker for reductive biotransformation of halothane and its associated toxicity.

UR - http://www.scopus.com/inward/record.url?scp=0018667794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018667794&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0018667794

VL - 51

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 3 SUPPL

ER -