Antiteratogenic effects of alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero.
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.
Jang
Ja Young
JY
College of Veterinary Medicine, Chungbuk National University, 12 Gaeshindong, Cheongju, Chungbuk, Republic of Korea.
Shin
Sunhee
S
Choi
Byong-Il
BI
Park
Dongsun
D
Jeon
Jeong Hee
JH
Hwang
Seock-Yeon
SY
Kim
Jong-Choon
JC
Kim
Yun-Bae
YB
Nahm
Sang-Seop
SS
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
D001571:Benzoflavones; D000072317:Polychlorinated Dibenzodioxins; D020011:Protective Agents; D013723:Teratogens; C011512:alpha-naphthoflavone