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

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Abstract
The effect of ellagic acid and some of its more lipophilk derivatives on the mutagenicity of (± )-7β, 8α-di-hydroxy-9α 10α-epoxy-7, 8, 910-etrahydrobenz[a]pyrene was examined in Salmonella typhimurium TA100. Ellagic acid, 3, 3' -di-O-methylellagic add, 4, 4' -di-O-methylellagic acid and 3-O-decyiellagic acid were found to have approximately equal antimutagenic activity. The tissue distribution and elimination of ellagic add, 3, 3' -di-O-methyleCagic add and 3-O-decylellagic acid were examined in CD-I mice. Little or no ellagic acid (< 1 nmol/g) was found in blood, lung or liver after the oral administration by gavage of 300 μunol of ellagic acid per kg body weight or after feeding 1% of ellagic acid in the diet for 1 week. Following the i.p. administration of 120 μmol/kg of ellagic acid, the blood and lung levels of ellagic acid were 15–20 nmol/g at 30 min after the dose, and the concentrations of ellagic acid decreased to 1–3 nmol/g at 6–8 h after the dose. A portion of the administered i.p. dose precipitated in the abdominal cavity. After i.v. administration, ellagic acid was eliminated very rapidly from blood, lung and liver, and ∼ 70% of the administered dose was recovered in the urine and feces as free ellagic acid and its conjugates. At 2 h after an i.v. injection of 60 μ/kg of ellagic add, 46% of the dose was recovered in the urine as ellagic acid and its conjugates. Of this amount, about half was excreted as free ellagic acid and half was excreted as conjugates. An additional 25% of the dose was recovered in the feces (mostly as free ellagic acid) after 7 h. The disposition of 3, 3' -di-O-methylelIagic acid or 3–O-decyIellagic acid after i.v. administration (32 μmol;sol;kg) was examined and compared to the disposition of the same i.v. dose of ellagic acid. The concentrations of ellagic acid, 3,3' -di-O-methylellagic acid and 3-O-decytellagic add decreased rapidly in the blood, liver and lung, but the concentrations of 3-O-decylellagic add in the lung throughout the experimental period (2–360 min) was on average 20- to 40-fold higher than the corresponding average concentrations of ellagic acid or 3, 3' -di-O-methylellagic acid.

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