In vivo and in vitro renal metabolism and excretion of benzoic acid by a marine teleost, the southern flounder.
In mammals, benzoic acid is primarily metabolized to its glycine conjugate, hippuric acid, which is readily excreted via the renal organic anion transport system. Teleost fish have not been shown to make glycine conjugates of carboxylic acids. Therefore, metabolism, excretion, and renal transport of benzoic acid were examined in the southern flounder, Paralichthys lethostigma. Excretion of injected [14C]benzoic acid was slow (10% of the administrated dose/day) and followed zero order kinetics. More than 95% of the excreted label was a single metabolite which was shown by hydrolysis and TLC to be benzoyltaurine. Isolated renal tubules and both hepatic and renal mitochondria produced benzoyltaurine in vitro. Excretion of benzoic acid and benzoyltaurine were not limited by plasma binding (less than 5% bound). To examine whether the slow excretion reflected renal transport, the transport of 100 microM benzoic acid, benzoyltaurine, and hippuric acid were determined in isolated renal tubules. All three compounds were accumulated via a probenecid- and cyanide-sensitive mechanism. Probenecid-sensitive uptake at 60 min of hippuric acid (436 nmol/mg) was greater than that of benzoyltaurine (164 nmol/mg) and both exceeded uptake of benzoic acid (63 nmol/mg). The same pattern was seen at 10 microM, except that tissue:medium ratios were even greater, indicating at least partial saturation of transport at 100 microM. Thus, the slow excretion of benzoic acid by these flounder was due to a combination of factors, including slow metabolism of benzoic acid to benzoyltaurine, saturation of the transport of benzoyltaurine, and low affinity of secretory transport for benzoic acid and benzoyltaurine, relative to hippuric acid, the mammalian metabolite.
D000818:Animals; D001565:Benzoates / Q000493:pharmacokinetics*; D019817:Benzoic Acid; D001693:Biological Transport, Active / Q000187:drug effects; D005412:Flatfishes / Q000378:metabolism*; D005432:Flounder / Q000378:metabolism*; D006626:Hippurates / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D007700:Kinetics; D008930:Mitochondria, Liver / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D012016:Reference Values; D013654:Taurine / Q000378:metabolism
D001565:Benzoates; D006626:Hippurates; D013654:Taurine; D019817:Benzoic Acid; D011339:Probenecid; C030514:hippuric acid