| ABSTRACT: |
|
The effect of ellagic acid and some of its more lipophilic derivatives
on the mutagenicity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10
alpha-epoxy-7,8,9,10-tetrahydrobenz[a]pyrene was examined in Salmonella
typhimurium TA100. Ellagic acid, 3,3'-di-O-methylellagic acid,
4,4'-di-O-methylellagic acid and 3-O-decylellagic acid were found to have
approximately equal antimutagenic activity. The tissue distribution and
elimination of ellagic acid, 3,3'-di-O-methylellagic acid and
3-O-decylellagic acid were examined in CD-1 mice. Little or no ellagic
acid (less than 1 nmol/g) was found in blood, lung or liver after the oral
administration by gavage of 300 mumol of ellagic acid per kg body weight
of after feeding 1% of ellagic acid in the diet for 1 week. Following the
i.p. administration of 120 mumol/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 approximately 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 mumol/kg of
ellagic acid, 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-methylellagic acid or 3-O-decylellagic acid
after i.v. administration (32 mumol/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-decylellagic acid
decreased rapidly in the blood, liver and lung, but the concentrations of
3-O-decylellagic acid 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. |