ascorbic-acid and methacetin

Hepatic mixed-function oxidase activity was measured in Gambian men during a period of low seasonal vitamin C intake and after vitamin C supplementation. Demethylation of methoxyphenylacetamide (methacetin) was followed using a breath test, in which the exhalation of 13C-enriched CO2 was measured following an oral dose of 13C-methacetin. Vitamin C supplementation, sufficient to increase plasma levels significantly, did not influence methacetin metabolism. However, methacetin metabolism in unsupplemented men appeared normal in the majority of cases. Hepatic tissue may not have been sufficiently depleted of vitamin C to impair the activity of the mixed function oxidase system.

Topics: Acetamides; Adult; Ascorbic Acid; Breath Tests; Carbon Dioxide; Drug Administration Schedule; Gambia; Humans; Liver; Male; Middle Aged; Mixed Function Oxygenases

Topics: Acetamides; Animals; Ascorbic Acid; Breath Tests; Carbon Isotopes; Guinea Pigs; Humans; Nutritional Requirements

Sodium vanadate inhibits the oxidative demethylation of substrates of the cytochrome P-450-dependent monooxygenase system in vivo in mice. [14C]Methacetin and 7-[methoxy-14C] coumarin were used as substrates, and the exhaled 14CO2 was monitored using the technique of the breath test. The inhibition is of short duration and begins to subside after about 10 min. The inhibition is dose-dependent; half-maximal effect is achieved at a dose of approximately 60 mumol/kg. The inhibition pattern is identical for both substrates, although 62% of the label of [14C] methacetin and only 10% of 7-[methoxy-14C] coumarin are enhaled within 1 h. Pretreatment with ascorbic acid (50 mg/kg p.o.) drastically diminishes the observed inhibitory effect of vanadate. Similarly, application of an equimolar dose of vanadyl sulphate produces a comparatively weak retardation of 14CO2 exhalation. The effect of vanadate is thought to occur by its competition for electrons normally transferred to cytochrome P-450.

Topics: Acetamides; Animals; Ascorbic Acid; Breath Tests; Carbon Dioxide; Coumarins; Cytochrome P-450 Enzyme Inhibitors; Dealkylation; Liver; Male; Mice; Oxidation-Reduction; Substrate Specificity; Vanadium