Green tea extract increases cyclophosphamide-induced teratogenesis by modulating the expression of cytochrome P-450 mRNA.
Reprod Toxicol
; 27(1): 79-84, 2009 Jan.
Article
in En
| MEDLINE
| ID: mdl-19103281
ABSTRACT
The effects of green tea extract (GTE) on the fetal development and external, visceral and skeletal abnormalities induced by cyclophosphamide were investigated in rats. Pregnant rats were daily administered GTE (100mg/kg) by gavage for 7 d, from the 6th to 12th day of gestation, and intraperitoneally administered with cyclophosphamide (11mg/kg) 1h after the final treatment. On the 20th day of gestation, maternal and fetal abnormalities were determined by Cesarian section. Cyclophosphamide was found to reduce fetal and placental weights without increasing resorption or death. In addition, it induced malformations in live fetuses; 94.6%, 41.5% and 100% of the external (skull and limb defects), visceral (cleft palate and ureteric dilatation) and skeletal (acrania, vertebral/costal malformations and delayed ossification) abnormalities. When pre-treated with GTE, cyclophosphamide-induced body weight loss and abnormalities of fetuses were remarkably aggravated. Moreover, repeated treatment with GTE greatly increased mRNA expression and activity of hepatic cytochrome P-450 (CYP) 2B, which metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard, while reducing CYP3A expression (a detoxifying enzyme). The results suggest that repeated intake of GTE may aggravate cyclophosphamide-induced body weight loss and malformations of fetuses by modulating CYP2B and CYP3A.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Teratogens
/
Abnormalities, Drug-Induced
/
RNA, Messenger
/
Plant Extracts
/
Aryl Hydrocarbon Hydroxylases
/
Cyclophosphamide
/
Camellia sinensis
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
Reprod Toxicol
Journal subject:
EMBRIOLOGIA
/
MEDICINA REPRODUTIVA
/
TOXICOLOGIA
Year:
2009
Document type:
Article