To evaluate the metabolic capacity of intact guinea pig liver under normoxic and hypoxic conditions, oxidative and reductive metabolism of
diphenyl sulfoxide (DPSO) was studied by the nonrecirculating perfusion method in situ. DPSO was exclusively converted into
diphenyl sulfone (DPSO2), an oxidative metabolite, under normoxia. When
diphenyl sulfide (DPS) was infused, DPSO was eliminated as a predominant metabolite. Judging from the susceptibility toward selective inhibitors of
cytochrome P-450, both oxidative steps appear to be catalyzed by
cytochrome P-450-dependent monooxygenase rather than
flavin adenine dinucleotide-containing
monooxygenase. Under hypoxic conditions, however, DPSO2 formation was decreased in parallel with reduced
oxygen concentration in the influent perfusate, whereas only a trace amount of DPS, a reductive metabolite, was detected. On the other hand, coinfusion of an electron donor for
aldehyde oxidase such as
2-hydroxypyrimidine and
benzaldehyde, but not
xanthine, markedly stimulated the formation of DPS during
hypoxia. These results indicate that the oxidative pathway catalyzed by
cytochrome P-450-dependent monooxygenase is predominant in DPSO metabolism under normoxic conditions, whereas only under
hypoxia does the reductive pathway become the major one if an electron donor for
aldehyde oxidase exists in intact guinea pig liver.