Synergistic Embryotoxicity of Combination Pyrimethamine and Folic Acid in Mice

마우스에 있어서 Pyrimethamine과 Folic acid의 병용에 의한 태아독성 상승효과

  • 정문구 (한국화학연구소 안정성연구센터) ;
  • 조규혁 (한국화학연구소 안정성연구센터) ;
  • 김종춘 (한국화학연구소 안정성연구센터) ;
  • 홍기창 (고려대학교 자연자원대학) ;
  • 한상섭 (한국화학연구소 안정성연구센터)
  • Published : 1996.12.01

Abstract

The increased embryotoxicity of the antifolate drug pyrimethamine (PYM) with concomitant dietary dosing of folic acid (FA) was examined in mice. The preventive effects of folinic acid (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM I (pyrimethamine 80 ppm), PYM II (pyrimethamine 150 ppm), PYM II+FNA (pyrimethamine 150 ppm and folinic acid 12 mg/kg/day), PYM II+FA (pyrimethamine 150 ppm and folic acid 350 ppm), FA (folic acid 350 ppm) and a control group. The agents were administered for 7 days from day 6 throughout 12 of gestation. PYM and FA were administered with mashed feed and FNA was intraperitoneally injected. The high incidence of fetal realformations was observed in the PYM II group; these included kinky tail, open eyelids, club foot, cleft palate, absence of the pulmonary lobe, diaphragmatic hernia, fused sternebrae, fused cervical or thoracic vertebral arch, among others. All embryos of the PYM II+FA group were resorbed. No realformed fetuses were observed in the PYM II+FNA group. These results show that the concomitant dosing of FA augments PYM embryotoxicity. The preventive effects of FNA were also observed.

Keywords

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