López del Pino V, Bolt H M
Arzneimittelforschung. 1977;27(11):2117-20.
Different kinds of experimental liver damage in rats are evaluated as to associated changes in breakdown of natural estrogens. Acute or chronic treatment of rats with ethanol does not influence aromatic hydroxylation of estradiol, as indicated by liver microsomal replacement of tritium from 2,4,6,7-3H-estradiol. More severe liver damage by CCl4 or thioacetamide, which lowers hepatic cytochrome P-450, causes impairment of estrogen degradation: CCl4 dosage leads to a marked decrease in aromatic hydroxylation of estradiol. Whereas thioacetamide in a chronic application schedule has been previously reported to a decrease microsomal aromatic estrogen hydroxylation, a single dose of 300 mg/kg thioacetamide in rats causes increased microsomal formation of estrone from estradiol, which is regarded to be a better (i.e., more lipophilic) substrate for the microsomal estrogen 2-hydroxylase than is estradiol. The data show that hepatotoxic agents may act differentially on hepatic metabolism of endogenous steroids.
对大鼠不同类型的实验性肝损伤，就天然雌激素分解的相关变化进行了评估。如通过肝微粒体从2,4,6,7 - ³H - 雌二醇中置换出氚所示，用乙醇对大鼠进行急性或慢性处理不会影响雌二醇的芳香族羟化作用。由四氯化碳（CCl₄）或硫代乙酰胺造成的更严重肝损伤会降低肝细胞色素P - 450，导致雌激素降解受损：CCl₄剂量会导致雌二醇芳香族羟化作用显著降低。虽然先前报道按慢性给药方案使用硫代乙酰胺会降低微粒体芳香族雌激素羟化作用，但在大鼠中单次给予300 mg/kg硫代乙酰胺会使雌二醇微粒体生成雌酮增加，与雌二醇相比，雌酮被认为是微粒体雌激素2 - 羟化酶更好的（即更具亲脂性的）底物。数据表明，肝毒性药物可能对内源性类固醇的肝脏代谢产生不同作用。
