联苯双酯对大鼠黄曲霉毒素B_1代谢及肝毒性的影响(英文)

EFFECTS OF DIMETHYL DIPHENYL BICARBOXYLATE ON THE METABOLISM AND HEPATOTOXICITY OF AFLATOXIN B_1 IN RATS

目的 研究抗肝炎药联苯双酯对大鼠黄曲霉毒素B1代谢和肝毒性的影响。方法 大鼠po联苯双酯 30 0mg·kg-1·d-1,连服 3d后ip黄曲霉毒素B11 5mg·kg-1。给黄曲霉毒素B116h后测定血清ALT和AST水平 ,观察联苯双酯对黄曲霉毒素B1引起肝损伤的保护作用以及对体外代谢的影响。结果 联苯双酯(30 0mg·kg-1·d-1,连服 3d)可明显降低黄曲霉毒素B1引起的大鼠血清转氨酶升高 ,增加低毒代谢产物AFM1的生成。联苯双酯还可增加大鼠肝脏细胞色素P4 5 0总量和胞浆GSH含量 ,诱导P4 5 0 2B1介导的PROD和GST的活性。此外 ,联苯双酯对P4 5 0 3A介导的红霉素脱甲基酶和P4 5 0 1A介导的EROD也有一定的诱导作用。结论 联苯双酯可通过增加大鼠肝脏对AFB1代谢的解毒功能起到肝保护作用。

AIM To study the effect of antihepatitis drug, dimethyl diphenyl bicarboxylate (DDB) on the metabolism and hepatotoxicity of aflatoxin B 1 (AFB 1) in rats. METHODS Rats were given orally DDB 300 mg·kg -1 ·d -1 for 3 days and then injected intraperitoneally with AFB 1 1 5 mg·kg -1 . Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined 16 hours after the injection of AFB 1. The in vitro metabolism of AFB 1 by DDB pretreated rat liver microsome was investigated by HPLC assay. RESULTS DDB (300 mg·kg -1 ) pretreatment provided significant protection against AFB 1 hepatotoxicity as evidenced by the decrease of AFB 1 elevated serum marker enzymes in rats. Pretreatment with DDB was shown to slightly increase the level of AFM 1, the less toxic metabolite. DDB significantly increased the liver cytochrome P450 content, P450 isozyme 2B 1 mediated 7 pentoxyresorufin O dealkylase (PROD) activity, cytosolic glutathione (GSH) level and GSH S transferase (GST) activities. In addition, DDB slightly increased P450 isozymes, 3A mediated erythromycin demethylase and 1A mediated 7 ethoxyresorufin O deethylase (EROD) activities. CONCLUSION The results indicate that DDB protected rats against AFB 1 hepatotoxicity by increasing the detoxifying metabolism of AFB 1 in the liver.