Reductive Drug Metabolism in Isolated Perfused Rat Liver under Restricted Oxygen Supply

Abstract

1. Hepatic azo and nitro reductase activities were studied in the perfused rat liver under normal and restricted oxygen supply.

2. Formation of sulphanilamide or p-aminobenzoic acid from neoprontosil or p-nitrobenzoic acid under aerobic conditions of liver perfusion was negligible, even at a reduced oxygen saturation of a pO₂ of 300 mm Hg in the haemoglobinfree perfusion syster… At a pO₂ of 200 mm Hg reductase activities were almost maximal.

3. Conjugation of sulphanilamide (0·08 mM) was similar under aerobic and anaerobic conditions. Hepatic elimination of p-aminobenzoic acid (0·08 mM) showed an oxygen-dependent increase for 15 min after addition of substrate.

4. p-Nitroanisole demethylation was inhibited 8% under hypoxic perfusion at 200 mm Hg pO₂ and was completely inhibited after gassing with anoxic mixtures.

5. Restitution of aerobic conditions after 30 min anaerobic perfusion restored hepatic respiration, lactate pyruvate ratio, and pH value to levels found under aerobic conditions, but bile flow remained 50% reduced.