USE OF THE [C-14] 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 obes e rats. To determine how these findings may affect hepatic drug metabo lizing activity, the aminopyrine breath test was performed in nine mal e dietary obese Sprague-Dawley rats weighing 440-460 g. Animals were m aintained on a VLED, and at 0, 14, and 21 d were injected with 9.25 k Bq (0.25 muCi) [dimethylamine-C-14]aminopyrine and placed in airtight restraining cages; exhaled (CO2)-C-14 was collected for 120 min. VLED animals had an increased half-life of exhaled (CO2)-C-14 (P < 0.01) an d a decreased rate constant of aminopyrine elimination (P < 0.01) cons istent with decreased N-demethylation of aminopyrine. Decreased liver glutathione suggests reduced ability to detoxify drugs through this co njugation pathway. These studies suggest that animals on VLEDs have re duced capacity for demethylation of aminopyrine as measured by oxidati ve elimination of (CO2)-C-14, and may exhibit decreased metabolism of other drugs.