CYCLOSPORINE-A HEPATOTOXICITY - EFFECT OF PROLONGED TREATMENT WITH CYCLOSPORINE ON BILIARY LIPID SECRETION IN THE RAT

被引：41

作者：

GALAN, AI ^{[1
]}

FERNANDEZ, E ^{[1
]}

MORAN, D ^{[1
]}

MUNOZ, ME ^{[1
]}

JIMENEZ, R ^{[1
]}

机构：

[1] UNIV SALAMANCA,DEPT PHYSIOL & PHARMACOL,E-37007 SALAMANCA,SPAIN

来源：

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | 1995年 / 22卷 / 04期

关键词：

BILIARY LIPID; CHOLESTASIS; CYCLOSPORINE A; HEPATOTOXICITY;

D O I：

10.1111/j.1440-1681.1995.tb01991.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The effects of cyclosporine A (CyA) treatment on liver morphology, bile flow and biliary secretion of bile acid, cholesterol and phospholipid and some plasma biochemical indicators of liver function were examined. 2. Wister rats were treated i.p. with 10 or 20 mg of CyA/kg per day for 1, 2, 3 or 4 weeks. 3. Treatment increased bile acid and bilirubin plasma concentration. Bile flow and biliary secretion of bile acid, cholesterol and phospholipid were reduced in CyA-treated animals. 4. All these effecs of the drug appeared at 1 week after the start of treatment and were enhanced during prolonged treatment. Cyclosporine A-induced cholestasis was due to a decrease in both the bile acid-dependent and -independent fractions of bile flow. 5. The reduction in cholesterol and phospholipid biliary output may be secondary to the inhibition of the hepatobiliary flux of bile acid; however, perturbations in the removal of lipids from the canalicular membrane as well as intracanalicular interaction between CyA and lipid vesicles/micelles could also be involved.

引用

页码：260 / 265

页数：6