Circadian rhythm of embryotoxicity induced by sodium valproate in mice

Shigehiro Ohdo , Hirokazu Watanabe , Nobuya Ogawa , Yuji Yoshiyama , Takashi Sugiyama
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引用次数: 17

Abstract

The influence of dosing time on embryotoxicity of valproate was investigated in ICR (Institute of Cancer Research, USA) mice under light-dark (12:12) cycle. A significant circadian rhythm was shown for embryotoxicity, with the highest value at 17:00 and the lowest at 01:00. No significant difference between injection at 17:00 and 01:00 was demonstrated for valproate concentrations in the embryo. The rhythm in the embryotoxicity seems to be related to the rhythm in the sensitivity to the drug. Embryotoxicity and valproate concentrations were significantly higher on gestational day 13 than day 7. The timing of drug administration (i.e, gestational stage and circadian phase) appears to be essential in the study of embryotoxicity of valproate in mice.

丙戊酸钠诱导小鼠胚胎毒性的昼夜节律
以美国癌症研究所ICR小鼠为实验对象,在光照-黑暗(12:12)周期下研究丙戊酸钠给药时间对胚胎毒性的影响。胚胎毒性表现出明显的昼夜节律,17:00时最高,01:00时最低。胚胎中丙戊酸盐浓度在17:00和01:00注射时无显著差异。胚胎毒性的节律似乎与药物敏感性的节律有关。胚胎毒性和丙戊酸浓度在妊娠第13天显著高于妊娠第7天。在研究丙戊酸对小鼠的胚胎毒性时,给药时间(即妊娠期和昼夜节律期)似乎是必不可少的。
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