Effects in rats of maternal exposure to raspberry leaf and its constituents on the activity of cytochrome p450 enzymes in the offspring.
The goal of our study was to determine whether maternal exposure to red raspberry leaf (RRL) and its constituents can permanently alter biotransformation of fluorogenic substrates by cytochrome P450 (CYP) in the livers of male and female offspring. Nulliparous female rats received vehicle, raspberry leaf, kaempferol, quercetin, or ellagic acid orally once breeding had been confirmed until parturition. Hepatic microsomes were prepared from animals at birth (postnatal day 1 [PND1]), weaning (PND21), PND65, and PND120 to determine the biotransformation of 8 fluorogenic substrates. The pattern of biotransformation of all but 2 of the substrates was gender specific. Maternal consumption of RRL increased biotransformation of 3 substrates by female offspring at PND120 resulting in a more masculine profile. Kaempferol and quercetin had a similar effect to RRL. These results suggest that maternal consumption of either RRL or some of its constituents leads to long-term alterations of CYP activity in female offspring.
Department of Obstetrics & Gynecology, McMaster University, Hamilton, Ontario, Canada.
Emilija
E
Makaji
Shirley H Y
SH
Ho
Alison C
AC
Holloway
Denis J
DJ
Crankshaw
D000367:Age Factors; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004610:Ellagic Acid / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D044949:Kaempferols / Q000009:adverse effects / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018811:Maternal Exposure; D018515:Plant Leaves / Q000737:chemistry*; D011794:Quercetin / Q000009:adverse effects / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D027824:Rosaceae / Q000737:chemistry; D012737:Sex Factors
D044949:Kaempferols; D004610:Ellagic Acid; C006552:kaempferol; D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin