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Inhibition of phenytoin bioactivation and teratogenicity by dietary n−3 fatty acids in mice
Author(s) -
Kubow Stan
Publication year - 1992
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536032
Subject(s) - linseed oil , chemistry , phenytoin , gestation , prostaglandin , teratology , medicine , endocrinology , biochemistry , pharmacology , pregnancy , biology , food science , genetics , neuroscience , epilepsy
Evidence suggests that the teratogenicity of the anticonvulsant drug phenytoin (DPH) can result from its bioactivation via embryonic prostaglandin synthase and/or maternal cytochromes P450. This study examined whether DPH bioactivation and teratogenicity could be reduced by dietary n−3 fatty acids. Female CD‐1 mice were fed diets containing 2 wt% safflower oil and 10 wt% of either hydrogenated coconut oil, safflower oil, or a cod liver oil/linseed oil mixture (CLO/LO) for three weeks prior to impregnation and throughout gestation. DPH (55 or 65 mg/kg) was administered via intraperitoneal injections to pregnant mice at 0900 on gestational days 12 and 13, and on day 19 fetuses were given teratologic assessments. A similar dietary study evaluated in vivo covalent binding of radiolabeled DPH administered on day 12, and dams were killed 24 h later. A reduction in DPH‐induced cleft palates and a decrease in DPH covalent binding to embryonic protein was observed in the CLO/LO group. Feeding CLO/LO enhanced incorporation of n−3 fatty acids into embryos and inhibited embryonic prostaglandin synthase activity. No differences in maternal hepatic cytochromes P450 activities were observed among dietary treatments. These data indicate that dietary n−3 fatty acids could reduce DPH teratogenicity via inhibition of embryonic prostaglandin synthase bioactivation of DPH.