Effect of phenobarbital sodium and 3-methylcholanthrene on metabolism in vitro and toxicity of $^{14}C$-carbofuran in rat

쥐에서 phenobarbital sodium 및 3-methylcholanthrene이 $^{14}C$-carbofuran의 독성과 in vitro 대사에 미치는 영향

  • Han, Seong-Soo (Department of Agricultural Chemistry, College of Life Science and Natural Resources, Wonkwang University) ;
  • Rim, Yo-Sup (Department of Agricultural Chemistry, College of Agriculture, Sunchon National University)
  • 한성수 (원광대학교 생명자원과학대학 농화학과) ;
  • 임요섭 (순천대학교 농과대학 농화학과)
  • Published : 1998.09.30

Abstract

In order to elucidate the effect of phenobarbital sodium(PB) and 3-methylcholanthrene(3-MC) on metabolism in vitro and toxicity of $^{14}C$-carbofuran in rat, they were administered by the chemicals, alone or in combination, and their survival ratios and metabolites were investigated. The $LD_{50}$(96 hrs) value of carbofuran to rats was 6.9 mg/kg. The toxicities of the major metabolites were in the decreasing order of 3-hydroxycarbofuran, 3-ketocarbofuran, 3-hydroxycarbofuran phenol and were much lower than that of the parent compound. When the rats were orally administered by the dose of carbofuran alone, 8.4 mg/kg, the survival ratio was 0%, whereas that was raised up to $60{\sim}80%$ with 20 mg/kg of PB or 3-MC, and 100% with 60 mg/kg of PB or 3-MC. Their metabolism in vitro occurred in the microsomal fraction. In case of carbofuran alone, the major metabolite was 3-hydroxycarbofuran. When carbofuran with PB or 3-MC, on the other hand, was treated, it was 3-ketocarbofuran. In addition, when the co-factor(NADP+G-6-P+G-6-P-DG) was added to the microsomal fraction(phase I system), and a mixture of NADPH+GSH to the 105,000g supernatant(phase II system) taken by carbofuran alone, each metabolites were produced by the maximum levels, respectively. In case of the carbofuran treatment with PB or 3-MC, the microsomal fraction of phase I system produced the maximum levels of metabolites, as in the treatment of carbofuran alone, whereas the 105,000g supernatant supplemented with the co-factor NADPH+FAD(phase II system) was brought about the maximum production of metabolites. The ratio of the formation of metabolites was 2 to 3 times higher in the combined treatment of carbofuran with PB or 3-MC than in the treatment of carbofuran alone.