Metabolism of trans-cinnamic acid in the rat and the mouse and its variation with dose.
The metabolism of [3-14C/phenyl-2H5] cinnamic acid was investigated in rats and mice at a dose level of 2.5 mmol/kg body weight. Recoveries of the 14C dose were between 92 and 98% with most (82-90%) present in the 0-24 hr urine samples. Urinary metabolites were identified by their chromatographic properties and mass spectra. In both species the major metabolite was hippuric acid, which is also an endogenous urinary component. Several minor metabolites, 3-hydroxy-3-phenylpropionic acid, benzoic acid and benzoyl glucuronide, were found in both species. Two, acetophenone and cinnamoylglycine, the glycine conjugate of cinnamic acid, could be positively identified only in mouse urine. The effect of dose size on the urinary excretion of 14C-cinnamic acid metabolites was studied over the dose range 0.0005 to 2.5 mmol/kg. In the rat the pattern of metabolite excretion was very similar over the whole dose range with slight increases in the proportion of the dose excreted as minor metabolites as dose size increased. In the mouse the excretion of cinnamoylglycine was more important at the lowest dose level and decreased in relative importance as dose size increased. Changes in the other metabolites were similar to those seen in the rat.
Nutley
B P
BP
Department of Pharmacology and Toxicology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Farmer
P
P
Caldwell
J
J
D000098:Acetophenones / Q000652:urine; D000284:Administration, Oral; D000818:Animals; D001565:Benzoates / Q000652:urine; D019817:Benzoic Acid; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D007274:Injections, Intraperitoneal; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010666:Phenylpropionates / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013237:Stereoisomerism
D000098:Acetophenones; D001565:Benzoates; D002934:Cinnamates; D010666:Phenylpropionates; C029010:cinnamic acid; C090448:cinnamoylglycine; C037620:benzoyl glucuronide; C031579:beta-hydroxyphenylpropionic acid; D019817:Benzoic Acid; C038699:acetophenone; D005998:Glycine