The effect of glutathione depletion on 14CO2 evolution from [14C]methyl-labeled aminopyrine in intact rats.
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 glutathione-depleted 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.
D000632:Aminopyrine / Q000378:metabolism*; D000818:Animals; D002245:Carbon Dioxide; D002250:Carbon Radioisotopes; D003864:Depression, Chemical; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D007659:Ketones / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D011659:Pulmonary Gas Exchange; D051381:Rats; D011919:Rats, Inbred Strains; D012997:Solvents / Q000494:pharmacology; D013997:Time Factors
D002250:Carbon Radioisotopes; D007659:Ketones; D008298:Maleates; D012997:Solvents; D000632:Aminopyrine; D002245:Carbon Dioxide; C018637:phorone; C014476:diethyl maleate; D005978:Glutathione