The effect of glutathione depletion on 14CO2 evolution from [14C] methyl-labeled aminopyrine in intact rats

Authors

  • Harshika S. Bhatt,

    1. Liver Unit, Department of Internal Medicine, University of Texas Health Science Center at Dallas, Southwestern Medical School, Dallas, Texas 75235
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  • Burton Combes M. D.

    Corresponding author
    1. Liver Unit, Department of Internal Medicine, University of Texas Health Science Center at Dallas, Southwestern Medical School, Dallas, Texas 75235
    • Department of Internal Medicine, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235
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Abstract

The effect of hepatic glutathione depletion on 14CO2 evolution from [14C]methyl-labeled aminopyrine was assessed in fed male Sprague-Dawley rats. Within 30 min of i.p. administration of either diethylmaleate or phorone, hepatic glutathione fell approximately 75 to 80% and remained depressed for the ensuing 120 min. [14C]Aminopyrine was i.p. administered 30 min after the glutathione-lowering agents (zero time) and exhaled 14CO2 was collected at 15-min intervals for the next 120 min. Parameters of 14CO2 exhalation including peak exhalation rate, cumulative exhalation from 0 to 120 min and the elimination rate constant were all impaired in glutathionedepleted rats. Metabolism of the [14C]methyl groups involves N-demethylation with formation of formaldehyde, oxidation to formate and conversion to 14CO2. Glutathione depletion did not affect CO2 evolution from i.p. administered formate or bicarbonate. The glutathione-dependent step presumably involves either or both generation of formaldehyde or its subsequent oxidation to formate.

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