Perphenazine により誘発されたラット胎児の口蓋裂に関する組織学的研究 : 特に二次口蓋の形成と血清中コルチコステロンとの関連について
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概要
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In order to investigate the pathogenesis of cleft palate induced by a neuroleptic drug of phenothiazine derivatives, SD-rat fetuses were treated with perphenazine hydrochloride (PPZ) and examined by light and electron microscopy. The levels of corticosterone in maternal serum also were measured. The fetuses from dams treated orally with 50mg/kg on days from 13 to 15 of gestation showed inhibition of growth and a high frequency (87.5%) of cleft palates with micrognathia. Fetal mortality, however, was not significantly increased in treated groups. The corticosterone levels in maternal serum were 836.3μg/dl after 3 hours of treatment and 856.0μg/dl after 8 hours of treatment. In contrast, dams treated with combined PPZ and metyrapone (25mg/kg, subcutaneously injected twice a day) had reduced corticosterone levels (248μg/dl after 3 hours and 411.8μg/dl after 8 hours of treatment). At day 16, the palatal shelves in control fetuse started to elevate horizontally. Two horizontal palatal shelves then contacted each other and began to fuse. Long microvilli and small spherical body were observed at the epithelial surfaces of medial edges of both palatal shelves before fusion. The palatal shelves of fetuses in PPZ-treated groups were still vertically oriented even on days 17-20. Like the control groups, long microvilli and small spherical body also were observed at the epithelial surfaces of the medial edges of both palatal shelves. In fetuses having cleft palates from dams treated with the combined use of PPZ and metyrapone, the degree of morphological abnormalities was milder than that induced by PPZ alone. These results suggest that the development of cleft palates induced by PPZ in rat fetuses is caused primarily by the increased corticosterone levels in maternal serum.
- 九州歯科学会の論文
- 1995-04-25