The role of the tissues and gut flora in the metabolism of [14C]homoprotocatechuic acid in the rat and rabbit

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Abstract
The fate of orally administered [carboxy-14C]3, 4-dihydroxyphenylacetic (homoprotocatechuic) acid has been studied in normal and neomycin-treated rats and rabbits. In normal rats about 93% of the dose (0·1 g/kg) is excreted in 13 days after dosing, although 80% is excreted in the urine within 2 days. In neomycin-treated rats 100% of the 14C is excreted in 13 days, 95% being in the urine within 2 days. The urinary metabolites in 44 hr in normal rats were unchanged homoprotocatechuic acid (55% of the dose), homovanillic acid (19%), m-hydroxyphenylacetic acid (6·5%) and p-hydroxyphenylacetic acid (1·4%). In neomycin-treated rats, homoprotocatechuic acid (70%) and homovanillic acid (22%) were found but the other two metabolites were virtually absent. In normal and neomycin-treated rabbits, the 14C was excreted in the urine almost quantitatively in 9 days. The same metabolites as in rats were excreted, but there was more m-hydroxybenzoic acid (14%) and less homovanillic acid (6%). In neomycin-treated rabbits the excretion of m- and p-hydroxyphenylacetic acids was suppressed. In the rat, the metabolism of homoprotocatechuic acid, as far as methylation, dehydroxylation and decarboxylation (Scheline, 1967) is concerned, is qualitatively similar to that of protocatechuic acid (Dacre & Williams, 1968). In the rabbit, however, there is little, if any, decarboxylation. Whilst methylation is a reaction of the tissues, dehydroxylation and decarboxylation appear to be carried out by gut micro-organisms.