Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Effects of Butylated Hydroxyanisole on Glutathione S-Transferases Activity and Cyclophosphamide-Induced Teratogenicity in Rats

랫드에서 Butylated Hydroxyanisole에 의한 Glutathione S-Transferases 유도 및 Cyclophosphamide로 유발된 기형에 대한 예방효과

  • 강현구 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 이창희 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 이기창 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 이지은 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 김하정 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 최은경 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 윤영원 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 김윤배 (충북대학교 수의과대학 및 동물의학연구소)
  • Published : 2003.09.01
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Abstract

Effects of repeated treatment with butylated hydroxyanisole (BHA) on the induction of glutathione S-transferases (GSTs) and teratogenicity of cyclophosphamide were investigated in rats. Pregnant rats were orally treated with BHA (50 mg/kg) for 7 days, from days 6 to 12 of gestation, and intraperitoneally challenged with cyclophosphamide (15 mg/kg) 2 hr after the final treatment. On day 20 of gestation, the maternal and fetal abnormalities were examined. Separately, a part of rats was sacrificed for the assay of hepatic and placental GSTs activities on day 12 of gestation following 7-day treatment with BHA. Cyclophosphamide, administered on day 12 of gestation, induced 43.2% of fetal death and resorption, and 100% of malformations in live fetuses, in contrast to low fetal resorption (8.7%) and malformations (8%) in control group. The malformations include cranial defect and exencephaly (100%), micrognathia and tongue extrusion (100%), limb defects (40%), renal pelvic dilatation (39%), and cleft palate (15%). Interestingly, BHA induced GSTs activities by 62% and 46% over the control in liver and placenta, respectively, and remarkably reduced the fetal resorption (13.9%) and malformations, resulting in 62% of cranial defect and exencephaly, 68% of micrognathia and tongue extrusion, 29% of limb defects, and 14% of renal pelvic dilatation. Taken together, it is suggested that a long-term pretreatment with BHA could substantially prevent fetuses from abortion and malformations following intrauterine exposure to teratogens including cyclophosphamide by inducing phase II antioxidant enzymes such as GSTs.

Keywords

References

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