Stimulatory Effect of Foreign Compounds on Ascorbic Acid Biosynthesis and on Drug-Metabolizing Enzymes

Abstract

PREVIOUS studies in rats have shown that drugs such as ‘Chloretone’, barbital, phenobarbital and amino-pyrine can stimulate the biosynthesis of L-ascorbic acid from glucose through the glucuronic acid pathway^1–3 as follows: Evidence for this has come from the observations that these drugs markedly increase the urinary excretion of L-ascorbic acid and that they stimulate the conversion of glucose-1-¹⁴C to labelled D-glucuronic acid, L-gulonic acid and L-ascorbic acid^3–5. In the present study the following compounds were also found to be potent in stimulating the biosynthesis of L-ascorbic acid: the antirheumatic drug: phenylbutazone, the muscular relaxant: orphenadrine (2-dimethylaminoethyl-2-methyl-benzhydryl ether), and the carcinogenic hydrocarbons: 3-methylcholanthrene, 1,2,5,6-dibenzanthracene and 3,4-benzpyrene. Phenylbutazone and orphenadrine in doses of 20–50 mgm./day for 4 days to adult rats produced about a 20-fold increase in L-ascorbic acid excretion. The striking effect of a single 10-mgm. dose of 3-methylcholanthrene on the urinary excretion of the vitamin is shown in Fig. 1. By 6 days after administration the urinary excretion was 50–75 times greater than the control value and in fact during the 19-day period about 140 mgm. of L-ascorbic acid was excreted. This represents a minimum value for the total L-ascorbic acid synthesized since the vitamin is extensively metabolized in the rat⁶.