Disposition of the naturally occurring antimutagenic plant phenol, ellagic acid, and its synthetic derivatives, 3-O-decylellagic acid and 3, 3'-di-O-methylellagic acid in mice

The effect of ellagic acid and some of its more lipophilk derivativeson the mutagenicity of (? )-7ß, 8-di-hydroxy-9 10-epoxy-7,8, 910-etrahydrobenza]pyrene was examined in Salmonella typhimuriumTA100. Ellagic acid, 3, 3' -di-O-methylellagic add, 4, 4' -di-O-methylellagicacid and 3-O-decyiellagic acid were found to have approximatelyequal antimutagenic activity. The tissue distribution and eliminationof ellagic add, 3, 3' -di-O-methyleCagic add and 3-O-decylellagicacid were examined in CD-I mice. Little or no ellagic acid (<1 nmol/g) was found in blood, lung or liver after the oral administrationby gavage of 300 µunol of ellagic acid per kg body weightor after feeding 1% of ellagic acid in the diet for 1 week.Following the i.p. administration of 120 µmol/kg of ellagicacid, the blood and lung levels of ellagic acid were 15–20nmol/g at 30 min after the dose, and the concentrations of ellagicacid decreased to 1–3 nmol/g at 6–8 h after thedose. A portion of the administered i.p. dose precipitated inthe abdominal cavity. After i.v. administration, ellagic acidwas eliminated very rapidly from blood, lung and liver, and 70% of the administered dose was recovered in the urine andfeces as free ellagic acid and its conjugates. At 2 h afteran i.v. injection of 60 µ/kg of ellagic add, 46% of thedose was recovered in the urine as ellagic acid and its conjugates.Of this amount, about half was excreted as free ellagic acidand half was excreted as conjugates. An additional 25% of thedose was recovered in the feces (mostly as free ellagic acid)after 7 h. The disposition of 3, 3' -di-O-methylelIagic acidor 3–O-decyIellagic acid after i.v. administration (32µmol;sol;kg) was examined and compared to the dispositionof the same i.v. dose of ellagic acid. The concentrations ofellagic acid, 3,3' -di-O-methylellagic acid and 3-O-decytellagicadd decreased rapidly in the blood, liver and lung, but theconcentrations of 3-O-decylellagic add in the lung throughoutthe experimental period (2–360 min) was on average 20-to 40-fold higher than the corresponding average concentrationsof ellagic acid or 3, 3' -di-O-methylellagic acid.