The Hepatic and Intestinal Metabolic Activities of P450 in Rats with Surgery- and Drug-Induced Renal Dysfunction
The Hepatic and Intestinal Metabolic Activities of P450 in Rats with Surgery- and Drug-Induced Renal Dysfunction
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手术和药物引起的肾功能障碍大鼠中 P450 的肝脏和肠道代谢活性
DOI：
10.1023/a:1026131216669
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发表时间：
2003
影响因子：
3.7
通讯作者：
Y. Hashimoto
中科院分区：
文献类型：
--
作者：
Hiromi Okabe;M. Hasunuma;Y. Hashimoto
AbstractPurpose。在手术和药物性肾功能不全的大鼠中，对P450的肝脏和肠道代谢活性进行了评估。
AbstractPurpose. The hepatic and intestinal metabolic activities of P450 were evaluated in rats with surgery- and drug-induced renal dysfunction.
Methods. Renal failure was induced by five-sixths nephrectomy (NR), bilateral ureter ligation (BUL), the intramuscular injection of glycerol (GL), and the intraperitoneal injection of cisplatin (CDDP). Phenytoin 4-hydroxylation, debrisoquine 4-hydroxylation, and testosterone 6β-hydroxylation were estimated to evaluate the metabolic activities of cytochrome P450 (CYP) 2C, 2D, and 3A, respectively.
Results. The hepatic CYP3A metabolic activities were decreased by 65.9% and 60.2% in NR and GL rats, respectively. The hepatic CYP2C metabolic activity was decreased by 48.8% in CDDP rats. No alteration in hepatic drug-metabolizing activities was observed in BUL rats. On the other hand, the intestinal CYP3A metabolic activity was weakly increased in GL rats but not significantly altered in NR, CDDP, and BUL rats.
Conclusions. This study suggested (a) that only selected P450 metabolic activity in the liver is decreased in renal failure, (b) that extent of the decrease in hepatic metabolic activities of P450 is dependent on the etiology of renal failure, and (c) that alteration of CYP3A metabolic activity in the intestine is not always correlated with that in the liver.
影响因子：
3.8
作者：
Giacomini,KM;Roberts,SM;Levy,G
通讯作者：
Levy,G