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目的:研究抗肝炎新药双环醇对大鼠黄曲霉毒素B_1(AFB_1)代谢和肝毒性的影响.方法:大鼠灌胃双环醇300 mg·kg~(-1)·d~(-1),连服三日后腹腔注射黄曲霉毒素B_1 1.5 mg·kg~(-1).给黄曲霉毒素B_1 16小时后观察双环醇对黄曲霉毒素B_1引起肝损伤的防护作用以及对体外代谢的影响.结果:双环醇(300 mg·kg~(-1)·d~(-1),连服三日)可明显降低黄曲霉毒素B_1引起的大鼠血清转氨酶和肝脏MDA的升高,增加低毒代谢产物AFQ_1的生成.双环醇还可增加大鼠肝脏细胞色素P450总量和胞浆谷胱甘肽含量,诱导P450 CYP2B1介导的7-戊氧基香豆素脱烃酶和谷胱甘肽疏基转移酶的活性.此外,双环醇对P450 CYP3A介导的红霉素脱甲基酶和 P450 CYP1A介导的7-乙氧基香豆素脱烃酶也有诱导作用.结论:双环醇可通过增加大鼠肝脏对AFB_1代谢的解毒功能起到肝保护作用.
OBJECTIVE: To study the effect of anti-hepatitis B bicyclol on aflatoxins B 1 metabolism and hepatotoxicity in rats.METHODS: Bicyclol was administered intragastrically in a dose of 300 mg · kg -1 · d -1, Aflatoxins B_1 1.5 mg · kg -1 was administered intraperitoneally after three days of oral administration.After 16 hours aflatoxin B 1, the protective effect of bicycloalcohol on aflatoxin B 1 -induced hepatic injury and its effect on metabolism in vitro were observed.Results : Bicyclol (300 mg · kg -1 · d -1 for 3 days) can significantly reduce the increase of serum aminotransferase and hepatic MDA induced by aflatoxin B 1 and increase the low toxic metabolites Production of AFQ_1 Bicyclol also increased total cytochrome P450 and cytoplasmic glutathione content in the liver of rats, induced P450 CYP2B1-mediated degradation of 7-pentoxycoumarin dehydrogenase and glutathione In addition, bicyclol also induced P450 CYP3A-mediated erythromycin demethylase and P450 CYP1A-mediated 7-ethoxycoumarin dehydrogenase.CONCLUSION: Bicyclol can be induced by Increasing liver detoxification of AFB 1 metabolism by rat liver can play a role in the protection of liver.