Toxic action of N-dimethylphosphinothioyl carbofuran by oxidative activation process

산화적 활성화 과정을 통한 N-dimethoxyphosphinothioyl carbofuran의 독성발현

  • Yang, Kyew-Wan (Agricultural Technical Research Institute, DongBu Hannong Chemical) ;
  • Lee, Seog-Jong (Division of Biological Environment, College of Agriculture and Life Sciences, Kangwon National University) ;
  • Kim, Song-Mun (Division of Biological Environment, College of Agriculture and Life Sciences, Kangwon National University) ;
  • Han, Dae-Sung (Division of Biological Environment, College of Agriculture and Life Sciences, Kangwon National University) ;
  • Hur, Jang-Hyun (Division of Biological Environment, College of Agriculture and Life Sciences, Kangwon National University)
  • 양규완 (동부한농화학(주) 농업기술연구소) ;
  • 이석종 (강원대학교 농업생명과학대학 자원생물환경학부) ;
  • 김성문 (강원대학교 농업생명과학대학 자원생물환경학부) ;
  • 한대성 (강원대학교 농업생명과학대학 자원생물환경학부) ;
  • 허장현 (강원대학교 농업생명과학대학 자원생물환경학부)
  • Published : 1998.09.30

Abstract

The bimolecular inhibition rate constants of carbofuran and N-dimethylphosphinothioyl carbofuran(PSC) to acetylcholinesterase(AChE) were $7.7{\times}10^{5}\;M^{-1}{\cdot}min^{-1}$ and $1.2{\times}10^{3}\;M^{-1}{\cdot}min^{-1}$, respectively. These results showed that PSC required a bioactivation process for its toxic action because it didn't inhibit the target enzyme effectively. The potency of PSC as an inhibitor of AChE increased when PSC and AChE were incubated with microsomes fortified with NADPH compared with microsome alone. Piperonyl butoxide(PBO) addition to these coupled systems greatly reduced the inhibition of the target enzyme by blocking the bioactivation process. In vivo inhibition study of mouse brain AChE, $I_{50}$ value for AChE was 28 mg/kg for PSC and the value increased to 57 mg/kg when PBO was pretreated. This result showed that cytochrome $P_{450}$ would also play a role in the bioactivation process of PSC in vivo. And conversioin of carbofuran from PSC was 55 % in a chemical oxidation system using meta-chloroperoxybenzoic acid. The oxidative activation of PSC to carbofuran was shown to be essential for showing its toxicological action and cytochrome $P_{450}$ was identified as an important enzyme which participated in this process.

Keywords

procarbamate;bioactivation;inhibition;acetylcholinesterase;cytochrome $P_{450}$