Distribution and metabolism of ellagic acid in the mouse following intraperitoneal administration

The distribution and metabolism of ellagic acid (EA), a naturally occurring plant phenolic compound with reported antimutagenic and anticarcinogenic activity, was investigated in mice following intraperitoneal injection. Male Swiss-Webster mice were given a single i.p. injection of [3H]EA and sacrificed at 15 min, 30 min, 60 min, 120 min and 24 h post-injection. At these times urine, blood and bile samples were obtained from each animal and various organs were removed, weighed and homogenized. Radioactivity in the samples was determined at each time interval and expressed as nmol [3H] EA/mg sample. Metabolites in urine and bile were analyzed by high-performance liquid chromatography (HPLC) and water-soluble conjugates were isolated by eluting samples of urine and bile from an alumina column. Radioactivity expressed as nmol [3H] EA/mg sample (wet weight) decreased with time in most organ homogenates. The peak radioactivity in bile appeared at 60 min post-injection while the peak radioactivity in urine occurred at 120 min. The two organs showing the highest amount of radioactivity were kidney and liver and the lowest was in brain. HPLC analysis revealed one unidentified metabolite of EA in bile and three in urine. Most of the radioactivity recovered from both bile and urine was associated with EA. Water-soluble conjugates in urine were isolated as sulfate esters, glucuronide and glutathione conjugates. Water-soluble conjugates in bile were evenly distributed as glucuronide and glutathione conjugates.