Effect of large doses of ascorbic acid on the mixed function oxidase system in guinea pig liver

Reports of the beneficial effects of large doses of ascorbic acid have stressed its water solubility and non-toxic properties. In this study male guinea pigs, dosed with 150 mg twice daily, ascorbic acid, demonstrated no differences in effect on liver weight, body weight or hepatic total protein when compared with controls. The activities of NADPH-dependent cytochrome c reductase, N-demethylase (Type I) and O-de-ethylase enzymes (Type II) remained unaffected, but the activity of the Type I hydroxylating enzyme, biphenyl-4-hydroxylase, and the amounts of cytochromes P-450 and b5 were significantly reduced. Total microsomal haem proteins were reduced and mirrored the effects in cytochromes P-450 and b5. The rate-limiting enzyme in haem synthesis, delta-amino-laevulinic acid synthetase, rose in the ascorbic acid group and this was associated with a fall in activity of the haem degrading enzyme, microsomal haem oxygenase. Thus, large amounts of ascorbic acid have similar effects to those found in scorbutic animals and appear to interfere with the construction of the cytochrome P-450 molecule.