Effects of ellagic acid by oral administration on distribution and metabolism of 2-aminofluorene in Sprague-Dawley rats.
The effects of ellagic acid on the in vivo N-acetylation and metabolism of 2-aminofluorene (2-AF) were investigated in bladder, blood, colon, kidney, liver, feces and urine samples from male Sprague-Dawley rats. Major metabolites such as 1-OH-2-AAF, 8-OH-2-AAF and 9-OH-2-AAF were found in bladder tissues, 1-OH-2-AAF, 5-OH-2-AAF and 8-OH-2-AAF were found in blood samples, 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF, 8-OH-2-AAF and 9-OH-2-AAF were found in colon tissues, 1-OH-2-AAF, 3-OH-2-AAF and 9-OH-2-AAF were found in kidney tissues, 1-OH-2-AAF, 3-OH-2-AAF and 8-OH-2-AAF were found in liver tissues, 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF and 8-OH-2-AAF were found in feces samples and 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF and 8-OH-2-AAF were also found in urine samples after rats had been orally treated with 2-AF (50 mg/kg) for 24 h. Pretreatment of male rats with ellagic acid (10 mg/kg) 24 h prior to the administration of 2-AF (50 mg/kg) resulted in absence of 8-OH-2-AAF in bladder tissues, and there were significant decreases of 8-OH-2-AAF in blood and urine samples. In blood samples, amounts of 2-AAF and 8-OH-2-AAF were significantly decreased; in colon tissues, amounts of 2-AF, 1-OH-2-AAF and 3-OH-2-AAF, in liver tissues, amounts of 2-AAF, 1-OH-2-AAF and 3-OH-2-AAF, and in urine samples, amounts of 2-AF and 8-OH-2-AAF were significantly decreased in 24-h ellagic acid (EA)-treated rats before 2-AF was added to the diet. However, significantly increased 1-OH-2-AAF concentrations were found in urine samples in 24-h EA-treated rats before 2-AF was administered. In the EA and 2-AF rats, in the same time treated groups, bladder, colon and liver tissues, and feces and urine samples showed significant differences when compared to the ones without EA co-treatment. We saw significant decreases of the amounts of 2-AF and 1-OH-2-AAF in colon tissues. The feces samples showed increased amounts of 2-AAF in EA- and in 2-AF- treated rats in the same time groups, but urine samples showed a decreased amount of 8-OH-2-AAF in both EA-treated groups. The total amounts of 2-AF metabolites in bladder, blood, kidney and liver tissues showed significant difference between control and the group which was EA-treated 24 h before 2-AF was added. The total amounts of 2-AF metabolites in the liver, feces and urine showed significant decreases between control and EA-treated at the same time with 2-AF groups. This is the first report of EA affecting the N-acetylation and metabolism of 2-AF in rat tissues in vivo.
Ho
Chin-Chin
CC
Department of Nursing, Chungtai Institute of Health Sciences and Technology, Takun, Taichung, Taiwan, ROC.
Lai
Yi-Shyong
YS
Wang
Der-Yean
DY
Chen
Yi-Shuan
YS
Lee
Jau-Hong
JH
Tang
Nou-Ing
NI
Chung
Jing-Gung
JG
D015073:2-Acetylaminofluorene / Q000032:analysis / Q000493:pharmacokinetics*; D000107:Acetylation / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D001711:Biotransformation; D002273:Carcinogens / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004610:Ellagic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008660:Metabolism / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D002273:Carcinogens; D004610:Ellagic Acid; D015073:2-Acetylaminofluorene