title: Antiteratogenic effects of alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero.
abstract: The effects of alpha-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist, on the reproductive toxicity and teratogenicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were investigated. Pregnant C57BL/6J mice were orally administered alpha-naphthoflavone either once on gestational day 12 (GD12; 50 microg/kg) or for 6 days (GD8-GD13; 5 mg/kg/day) followed by an oral challenge with TCDD (14 microg/kg) on GD12. Cesarean section was performed on GD18 for the evaluation of maternal and fetal toxicities. TCDD caused severe fetal malformations including cleft palate (43.7%) and renal pelvic and ureteric dilatations (100%). The administration of alpha-naphthoflavone either in a single treatment or 6-days remarkably reduced the incidence of cleft palate to 27.6% and 26.5%, respectively. In addition, the degree of renal pelvic and ureteric dilatations caused by TCDD were significantly attenuated by repeated treatment of alpha-naphthoflavone. These results suggest that AhR antagonists such as alpha-naphthoflavone could be promising candidates for reducing the incidence and severity of fetal malformations caused by TCDD exposure in utero.
authors: College of Veterinary Medicine, Chungbuk National University, 12 Gaeshindong, Cheongju, Chungbuk, Republic of Korea.
authors: Ja Young
authors: JY
authors: Jang
authors: Sunhee
authors: S
authors: Shin
authors: Byong-Il
authors: BI
authors: Choi
authors: Dongsun
authors: D
authors: Park
authors: Jeong Hee
authors: JH
authors: Jeon
authors: Seock-Yeon
authors: SY
authors: Hwang
authors: Jong-Choon
authors: JC
authors: Kim
authors: Yun-Bae
authors: YB
authors: Kim
authors: Sang-Seop
authors: SS
authors: Nahm
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000473:pathology / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002972:Cleft Palate / Q000139:chemically induced / Q000196:embryology / Q000517:prevention & control; D004336:Drug Antagonism; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000196:embryology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011247:Pregnancy; D020011:Protective Agents / Q000494:pharmacology*; D013723:Teratogens / Q000633:toxicity*; D014513:Ureter / Q000002:abnormalities / Q000187:drug effects; D014515:Ureteral Diseases / Q000139:chemically induced / Q000196:embryology / Q000517:prevention & control
chemical_list: D001571:Benzoflavones; D000072317:Polychlorinated Dibenzodioxins; D020011:Protective Agents; D013723:Teratogens; C011512:alpha-naphthoflavone