Chung M K, Han S S, Roh J K
Toxicology Research Center, Korea Research Institute of Chemical Technology, Daedeog-Danji, Daejeon.
Reprod Toxicol. 1993 Sep-Oct;7(5):463-8. doi: 10.1016/0890-6238(93)90091-k.
The increased embryotoxicity of pyrimethamine (PYM) with concomitant oral dosing of folic acid (FA) was examined in rats. The preventive effects of folinic acid (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM I (PYM 1.2 mg/kg/day), FA (FA 50 mg/kg/day), PYM I+FA (1.2 and 50 mg/kg/day, respectively), PYM II (2.7 mg/kg/day), PYM II+FNA (2.7 and 12 mg/kg/day, respectively), and a vehicle control group. The agents were administered for 11 days from day 7 throughout 17 of gestation. PYM and FA were administered by gavage and FNA was administered intraperitoneally. Visceral and skeletal malformations were observed in the fetuses of both PYM I+FA and PYM II groups; these included dilatation of the lateral ventricle and fused ribs. No malformed fetuses were observed in the fetuses of the other four groups. External malformations were observed only in the fetuses of PYM II groups; these included cleft palate, cleft lips, and brachygnathia, among others. These results show that the concomitant gavage dosing of FA augments PYM embryotoxicity. The preventive effects of FNA were also confirmed.
在大鼠中研究了乙胺嘧啶（PYM）与叶酸（FA）同时口服给药时胚胎毒性的增加情况。还研究了亚叶酸（FNA）对PYM胚胎毒性的预防作用。构建了六组：PYM I组（PYM 1.2毫克/千克/天）、FA组（FA 50毫克/千克/天）、PYM I+FA组（分别为1.2和50毫克/千克/天）、PYM II组（2.7毫克/千克/天）、PYM II+FNA组（分别为2.7和12毫克/千克/天），以及一个溶剂对照组。从妊娠第7天至第17天，连续11天给药。PYM和FA通过灌胃给药，FNA通过腹腔注射给药。在PYM I+FA组和PYM II组的胎儿中均观察到内脏和骨骼畸形；这些畸形包括侧脑室扩张和肋骨融合。在其他四组胎儿中未观察到畸形胎儿。仅在PYM II组的胎儿中观察到外部畸形；这些畸形包括腭裂、唇裂和小颌畸形等。这些结果表明，FA同时灌胃给药会增强PYM的胚胎毒性。FNA的预防作用也得到了证实。
