Document Detail

Green tea extract increases cyclophosphamide-induced teratogenesis by modulating the expression of cytochrome P-450 mRNA.
MedLine Citation:
PMID:  19103281     Owner:  NLM     Status:  MEDLINE    
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.
Dongsun Park; Jeong Hee Jeon; Sunhee Shin; Seong Soo Joo; Dae-Hyuck Kang; Seol-Hee Moon; Min-Jung Jang; Yeoung Mi Cho; Jae Wook Kim; Hyeong-Jin Ji; Byeongwoo Ahn; Ki-Wan Oh; Yun-Bae Kim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-03
Journal Detail:
Title:  Reproductive toxicology (Elmsford, N.Y.)     Volume:  27     ISSN:  0890-6238     ISO Abbreviation:  Reprod. Toxicol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-02-02     Completed Date:  2009-04-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803591     Medline TA:  Reprod Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-84     Citation Subset:  IM    
College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, 410 Seongbongro (Gaeshin-dong), Cheongju, Chungbuk 361-763, Republic of Korea.
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MeSH Terms
Abnormalities, Drug-Induced*
Aryl Hydrocarbon Hydroxylases / biosynthesis*,  genetics
Camellia sinensis / chemistry*
Cyclophosphamide / toxicity*
Cytochrome P-450 CYP2B1 / biosynthesis,  genetics
Cytochrome P-450 CYP3A / biosynthesis,  genetics
Drug Synergism
Fetal Development / drug effects,  physiology
Gene Expression Regulation, Developmental / drug effects
Microsomes, Liver / drug effects,  enzymology
Plant Extracts / pharmacology*
RNA, Messenger / drug effects*,  metabolism
Rats, Sprague-Dawley
Teratogens / toxicity*
Reg. No./Substance:
0/Plant Extracts; 0/RNA, Messenger; 0/Tea; 0/Teratogens; 50-18-0/Cyclophosphamide; EC Hydrocarbon Hydroxylases; EC P-450 CYP2B1; EC P-450 CYP3A

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