Effects of ellagic acid by oral administration on N-acetylation and metabolism of 2-aminofluorene in rat brain tissues

Numerous studies have demonstrated that the Acetyl Coenzyme A-dependent arylamine NAT enzyme exist in many tissues of experimental animals including humans, and that NAT has been shown to be exist in mouse brain tissue. Increased NAT activity levels are associated with increased sensitivity to the mutagenic effects of arylamine carcinogens. Attenuation of liver NAT activity is related to breast and bladder cancer processes. Therefore, the effects of ellagic acid (EA) on the in vitro and in vivo N-acetylation of 2-aminofluorene (AF) were investigated in cerebrum, cerebellum and pineal gland tissues from male Sprague-Dawley rats. For in vitro examination, cytosols with or without EA (0.5-500 microM) co-treatment decreased 7-72%, 15-63% and 10-78% of AF acetylation for cerebrum, cerebellum and pineal gland tissues, respectively. For in vivo examination, EA and AF at the same time treated groups with all 3 examined tissues did show significant differences (the changes of total amounts of AF and AF metabolites based on the Anova analysis) when compared to the ones without EA cotreatment rats. The pretreatment of male rats with EA (10 mg/kg) 24 hr prior to the administration of AF (50 mg/kg) (one day of EA administration suffice to induce large changes in phase II enzyme activity) resulted in a 76% decrease in total AF and metabolites in pineal gland but did not show significant differences in cerebrum and cerebellum tissues. This is the first demonstration to show that EA decreases the N-acetylation of carcinogens in rat brain tissues.