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Title: Effect of glutathione depletion on UCO2 evolution from ( UC)methyl-labeled aminopyrine in intact rats

Journal Article · · Hepatol.; (United States)

The effect of hepatic glutathione depletion on UCO2 evolution from ( UC)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. ( UC)Aminopyrine was i.p. administered 30 min after the glutathione-lowering agents (zero time) and exhaled UCO2 was collected at 15-min intervals for the next 120 min. Parameters of UCO2 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 ( UC)methyl groups involves N-demethylation with formation of formaldehyde, oxidation to formate and conversion to UCO2. 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.

Research Organization:
Univ. of Texas Health Science Center, Dallas
OSTI ID:
6335612
Journal Information:
Hepatol.; (United States), Vol. 4
Country of Publication:
United States
Language:
English