Antiteratogenic effects of α-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero
Antiteratogenic effects of α-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero
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DOI：
10.1016/j.reprotox.2007.08.002
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发表时间：
2007-11-01
影响因子：
3.3
通讯作者：
Nahm, Sang-Seop
中科院分区：
文献类型：
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作者：
Jang, Ja Young;Shin, Sunhee;Nahm, Sang-Seop
研究了芳烃受体（AhR）拮抗剂α-萘甲酮对2，3，7，8-四氯二苯并-对-二恶英（TCDD）生殖毒性和致畸性的影响。在妊娠第12天（GD 12; 50 μ g/kg）或6天（GD 8-GD 13; 5 mg/kg/天）经口给予妊娠C57 BL/6 J小鼠α-萘烷酮，然后在GD 12口服TCDD（14 μ g/kg）。在GD 18进行剖宫产，以评价母体和胎仔毒性。TCDD可引起严重的胎儿畸形，包括腭裂（43.7%）和肾盂输尿管畸形（100%）。单次或连续6天给予α-萘酮可显著降低腭裂的发生率，分别为27.6%和26.5%。此外，α-萘啶酮重复治疗可明显减轻TCDD引起的肾盂和输尿管扩张程度。这些结果表明，AhR拮抗剂，如α-萘烷酮可能是有前途的候选人，减少TCDD暴露在子宫内引起的胎儿畸形的发病率和严重程度。(C)2007爱思唯尔公司All rights reserved.
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 mu g/kg) or for 6 days (GD8-GD13; 5 mg/kg/day) followed by an oral challenge with TCDD (14 mu g/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. (C) 2007 Elsevier Inc. All rights reserved.