한국연초학회지 (Journal of the Korean Society of Tobacco Science)

한국연초학회 (The Korean Society of Tobacco Science)
권호 표지

Effect of Cigarette Smoke Exposure on MPTP Metabolism in the Liver of Mice

  • Heung Bin Lim (Laboratory of Biochemistry) ;
  • Ja Young Moon (Laboratory of Biochemistry, Korea Ginseng and Tobacco Research Institute) ;
  • Hyung Ok Sohn (Laboratory of Biochemistry, Korea Ginseng and Tobacco Research Institute) ;
  • Young Gu Lee (Laboratory of Biochemistry, Korea Ginseng and Tobacco Research Institute) ;
  • Dong Wook Lee (Laboratory of Biochemistry, Korea Ginseng and Tobacco Research Institute)
  • 발행 : 1998.06.01
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초록

Numerous studies have demonstrated a negative association between cigarette smoking and Parkinson's disease. The present study was undertaken to investigate whether chronic exposure of mice to cigarette smoke a(footed the metabolism of 1-methyl-1113,6-tetrahydro-pyridine (MPTP) by cytochrome P4SO (P-450) or flavin-containing monooxygenase (FMO) in the hepatic microsomes of C57BL6/J mice. Adult male C57BL6/J mice were exposed to mainstream smoke generated from 15 cigarettes for 10 min a day and 5 day per week for 6 weeks. MPTP (10 mg/kg body weight) was administered to mice by subcutaneous injection for 6 consecutive days. Microsolnal P-450 content was increased by MPTP, smoke exposure, or both, but NADPH cytochrome P-450 reductase activity was rather decreased by the same treatments. The activities of benzo(a)pyrene hydroxylase, 7-ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase were significantly increased by the exposure of cigarette smoke, but were not or little affected by MPTP treatment. Benzphetamine N-demethylase activity was not affected either by MPTP treatment or by cigarette smoke exposure, but it was significantly increased by the combined MPTP treatment with cigarette smoke exposure, showing their synergic effect for the induction of the enzyme activity. Interestingly, in vitro studies of hepatic FMO and P-450 system both O-oxygenation and N-demethylation of MPTP were increased in the smoke-exposed or in the MPTP-treated mice. These results suggest that the enhancement in the N-demethylation as well as O-deethylation of P-450 system and in the N-oxygenation of FMO activity by cigarette smoke exposure in mouse liver may contribute to attenuating the neurotoxic effects of MPTP on the nigrostriatal dopaminergic neurons.

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