Jang Ja Young, Shin Sunhee, Choi Byong-Il, Park Dongsun, Jeon Jeong Hee, Hwang Seock-Yeon, Kim Jong-Choon, Kim Yun-Bae, Nahm Sang-Seop
College of Veterinary Medicine, Chungbuk National University, 12 Gaeshindong, Cheongju, Chungbuk, Republic of Korea.
Reprod Toxicol. 2007 Nov-Dec;24(3-4):303-9. doi: 10.1016/j.reprotox.2007.08.002. Epub 2007 Aug 19.
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.
研究了芳基烃受体（AhR）拮抗剂α-萘黄酮对2,3,7,8-四氯二苯并对二恶英（TCDD）诱导的生殖毒性和致畸性的影响。将怀孕的C57BL/6J小鼠在妊娠第12天（GD12；50微克/千克）口服给予α-萘黄酮一次，或在妊娠第8天至第13天（GD8-GD13；5毫克/千克/天）连续口服6天，然后在GD12口服给予TCDD（14微克/千克）进行激发。在GD18进行剖宫产以评估母体和胎儿毒性。TCDD导致严重的胎儿畸形，包括腭裂（43.7%）和肾盂及输尿管扩张（100%）。单次给予α-萘黄酮或连续6天给药，腭裂发生率分别显著降低至27.6%和26.5%。此外，重复给予α-萘黄酮可显著减轻TCDD引起的肾盂及输尿管扩张程度。这些结果表明，α-萘黄酮等AhR拮抗剂有望成为降低子宫内暴露于TCDD所致胎儿畸形发生率和严重程度的候选药物。
