Use of the [14C]aminopyrine breath test to assess the hepatic response of dietary obese rats to a very-low-energy diet.
The intake of a very-low-energy diet (VLED) complete in all essential nutrients decreases liver mass and total liver protein in dietary obese rats. To determine how these findings may affect hepatic drug metabolizing activity, the aminopyrine breath test was performed in nine male dietary obese Sprague-Dawley rats weighing 440-460 g. Animals were maintained on a VLED, and at 0, 14, and 21 d were injected with 9.25 k Bq (0.25 microCi) [dimethylamine-14C]aminopyrine and placed in airtight restraining cages; exhaled 14CO2 was collected for 120 min. VLED animals had an increased half-life of exhaled 14CO2 (P < 0.01) and a decreased rate constant of aminopyrine elimination (P < 0.01) consistent with decreased N-demethylation of aminopyrine. Decreased liver glutathione suggests reduced ability to detoxify drugs through this conjugation pathway. These studies suggest that animals on VLEDs have reduced capacity for demethylation of aminopyrine as measured by oxidative elimination of 14CO2, and may exhibit decreased metabolism of other drugs.
Young
E A
EA
Department of Medicine, University of Texas Health Science Center, San Antonio.
Harris
M M
MM
Cantu
T L
TL
Deneke
S M
SM
Schenker
S
S
D000632:Aminopyrine; D000818:Animals; D001944:Breath Tests; D002250:Carbon Radioisotopes; D004032:Diet; D004038:Diet, Reducing; D002149:Energy Intake; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis
D002250:Carbon Radioisotopes; D000632:Aminopyrine; D005978:Glutathione