The role of the tissues and gut micro-organisms in the metabolism of [14C]protocatechuic acid in the rat. Aromatic dehydroxylation

Abstract

Abstract The fate of oral doses (0·1 g/kg) of [carboxy-14C]3, 4-dihydroxybenzoic (protocatechuic) acid in normal and neomycin-treated rats has been studied. In normal rats about 72% of the dose of 14C is excreted in 7 days (about 64% in urine and 8% in faeces) whereas in neomycin-treated rats 99% is excreted (87% in urine and 12% in faeces). In normal rats, the radioactive metabolites found in the urine excreted in 24 hr after dosing were protocatechuic acid (36%), vanillic acid (21%), m-hydroxybenzoic acid (2·1%), p-hydroxybenzoic acid (1·2%) and m-methoxybenzoic acid (2%). After neomycin-treatment protocatechuic acid (55%) and vanillic acid (22%) were found, but the other three were virtually absent. Incubation of [14C]protocatechuic acid with rat intestinal contents yielded 14CO2 and small amounts of m- and p-hydroxybenzoic acid. When [14C]protocatechuic acid was injected intraperitoneally into biliary cannulated rats about 13% appeared in the bile mainly as the 4-O-glucuronide of vanillic acid. It is concluded that, whilst the conjugation and methylation of protocatechuic acid occurs in the tissues of the rat, the dehydroxylation and decarboxylation of the acid is carried out by the gut micro-organisms.