Effect of acetone on the activation of acetaminophen

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Abstract

Isolated hepatocytes from phenobarbital-treated rats catalyzed the formation of three major metabolites from acetaminophen, a glucuronide, a sulfate, and a glutathione conjugate. Acetone at moderate concentrations caused a threefold increase in the glutathione conjugate formation, but the two other reactions were unaffected. This increase was due to an enhancement of the cytochrome P-450-dependent activation of acetaminophen and was observed also in microsomes supplemented with NADPH and glutathione. The increased activation of acetaminophen resulted in a loss of viability of the isolated hepatocytes after 3 hr of incubation. In the absence of acetone no loss of viability was observed. Acetone also caused an increased acetaminophen-glutathione conjugate formation in isolated hepatocytes from control rats whereas in isolated hepatocytes from mice, this reaction was almost unaffected.

References (23)

  • J.M. Hassing et al.

    Acetaminophen induced glutathione depletion in diabetic rats

    Res. Commun. Chem. Pathol. Pharmacol.

    (1979)
  • Cited by (20)

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    Present address: Chionin Pharm. Work Ltd., Department of Toxicology, 1045 Budapest, Hungary.

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