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Effects of Butylated Hydroxyanisole on Glutathione S-Transferases Activity and Cyclophosphamide-Induced Teratogenicity in Rats  

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)
Publication Information
Toxicological Research / v.19, no.3, 2003 , pp. 181-187 More about this Journal
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
Butylated hydroxyanisole (BHA); Glutathione S-transferases (GSTs); Cyclophosphamide; Teratogenicity;
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Times Cited By KSCI : 1  (Citation Analysis)
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