약학회지 (YAKHAK HOEJI)

  • 제44권5호
  • /
  • Pages.379-383
  • /
  • 2000
  • /
  • 0377-9556(pISSN)
  • /
  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Polychlorinated biphenyl 전처리한 횐쥐 간장의 S-9 분획에서 Stanozolol의 Hydroxylation 대사체의 생성

In vitro Metabolism of Stanozolol to 3'-Hydroxystanozolol in the Liver S-9 Fraction of Polychlorinated Biphenyl-treated Rats

  • 권오승 (한국과학기술연구원 생체대사연구센터 독성연구실) ;
  • 류재천 (한국과학기술연구원 생체대사연구센터 독성연구실)
  • 발행 : 2000.10.01
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초록

Stanozolol (STZ, 17$\alpha$-methyl-17$\beta$-hydroxy-5$\alpha$-androstano-(3,2-c) pyrazole), an anabolic steroid, is an abused drug by body-builders or atheletes, as well as medicine for treatment of aplastic anemia and vascular thrombosis. In human volunteers, the major urinary metabolite of STZ was reported to be 3'-hydroxystanozolol that was identified by gas chromatography-mass selective detector (GC/MSD). The objective of this experiment is to investigate the in vitro metabolism of STZ in liver S-9 faction of polychlorinated biphenyl-induced rats. Reaction mixture including STZ as substrate and the S-9 faction was extracted with diethyl ether and quantified by the selected ion monitoring mode of GC/MSD. The selected concentration of substrate STZ is 100 nmole and the selected time for incubation in the reaction mixture was determined to 60 min. The amount of 3'-hydroxystanozolol produced was increased by about 6-fold in the reaction medium including the liver S-9 fraction of polychlorinated biphenyl-induced rats, compared to that of untreated rats. Inhibitors of cytochrome P450, SKF-525A and 7,8-benzoflavone, decreased the production of 3'-hydroxystanozolol by about 89~100% and 65~75%, respectively; In conclusion, hydroxylation of STZ into 3'-hydroxystanozolol is confirmed by GC/MSD and is catalyzed by cytochrome P450.

키워드

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