Antiteratogenic effects of alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposed mice in utero |
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Authors: | 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 |
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Affiliation: | College of Veterinary Medicine, Chungbuk National University, 12 Gaeshindong, Cheongju, Chungbuk, Republic of Korea. |
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Abstract: | The effects of α-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 α-naphthoflavone either once on gestational day 12 (GD12; 50 μg/kg) or for 6 days (GD8–GD13; 5 mg/kg/day) followed by an oral challenge with TCDD (14 μg/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 α-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 α-naphthoflavone. These results suggest that AhR antagonists such as α-naphthoflavone could be promising candidates for reducing the incidence and severity of fetal malformations caused by TCDD exposure in utero. |
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Keywords: | 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Malformation Cleft palate Renal pelvic and ureteric dilatations Aryl hydrocarbon receptor (AhR) antagonist α -Naphthoflavone |
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