Polychlorinated biphenyl 전처리한 흰쥐 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

Stanozolol (STZ, 17alpha-methyl-17beta-hydroxy-5alpha-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 fraction of polychlorinated biphenyl-induced rats. Reaction mixture including STZ as substrate and the S-9 fraction was extracted with diethyl ether and quantified by the selected ion monitoring mode of GC/MSD. The selected concentration of substrate STZ is 100nmole 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.