title: Licorice extract increases cyclophosphamide teratogenicity by upregulating the expression of cytochrome P-450 2B mRNA.
abstract: BACKGROUND
  Since cyclophosphamide is metabolically activated to teratogenic acrolein and cytotoxic phosphoramide mustard by cytochrome P-450 type 2B (CYP2B), we assessed the effects of licorice, a CYP2B inducer, on the fetal defects induced by cyclophosphamide.
  
  
  METHODS
  Pregnant Sprague-Dawley rats were daily administered with licorice (100 mg/kg) by gavage for 7 days, from the 6th to 12th day of gestation, and intraperitoneally administered with cyclophosphamide (11 mg/kg) 1 hr after the final licorice treatment. On the 20th day of gestation, maternal and fetal abnormalities were determined by Cesarian section.
  
  
  RESULTS
  Cyclophosphamide was found to reduce fetal and placental weights without increasing resorption or death. In addition, it induced malformations in live fetuses; 93.8, 41.1, 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, respectively. When pre-treated with licorice, cyclophosphamide-induced body weight loss and abnormalities of fetuses were remarkably aggravated. Moreover, repeated treatment with licorice greatly increased mRNA expression and activity of hepatic CYP2B.
  
  
  CONCLUSIONS
  The results indicate that repeated intake of licorice may aggravate cyclophosphamide-induced body weight loss and malformations of fetuses by upregulating CYP2B.
authors.affiliation: College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Dongsun
authors.initials: D
authors.lastname: Park
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Yang
authors.forename: Ehn-Kyoung
authors.initials: EK
authors.lastname: Choi
authors.forename: Goeun
authors.initials: G
authors.lastname: Yang
authors.forename: Dae-Kwon
authors.initials: DK
authors.lastname: Bae
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Tae Kyun
authors.initials: TK
authors.lastname: Kim
authors.forename: Jangbeen
authors.initials: J
authors.lastname: Kyung
authors.forename: Dajeong
authors.initials: D
authors.lastname: Kim
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Yun-Bae
authors.initials: YB
authors.lastname: Kim
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity*; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry*; D010936:Plant Extracts / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D018906:Antineoplastic Agents, Alkylating; D010936:Plant Extracts; D012333:RNA, Messenger; D013723:Teratogens; D003520:Cyclophosphamide; D019362:Cytochrome P-450 CYP2B1