Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants

被引:149
作者
Mitsuyoshi, H [1 ]
Nakashima, T [1 ]
Sumida, Y [1 ]
Yoh, T [1 ]
Nakajima, Y [1 ]
Ishikawa, H [1 ]
Inaba, K [1 ]
Sakamoto, Y [1 ]
Okanoue, T [1 ]
Kashima, K [1 ]
机构
[1] Kyoto Prefectural Univ Med, Dept Internal Med 3, Kyoto 6028566, Japan
关键词
D O I
10.1006/bbrc.1999.1403
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The therapeutic efficacy of ursodeoxycholic acid (UDCA) has been widely demonstrated in various liver diseases, suggesting that UDCA might protect hepatocytes against common mechanisms of liver damage. A candidate for such protection is oxidative injury induced by reactive oxygen species. This study was designed to assess the effects of UDCA on oxidative injury and antioxidative systems in cultured rat hepatocytes. The viability of the hepatocytes dose-dependently decreased after hydrogen peroxide or cadmium administration. Pretreatment with UDCA significantly prevented this decrease in viability. The amounts of glutathione (GSH) and protein thiol increased significantly, but the activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and catalase were unchanged in UDCA-treated hepatocytes. The mRNA levels of gamma-glutamylcysteine synthetase and metallothionein (NIT) were significantly higher in UDCA-treated hepatocytes than in controls. In conclusion, UDCA increased hepatocyte levels of GSH and thiol-containing proteins such as MT, thereby protecting hepatocytes against oxidative injury. Our results provide a new perspective on the hepatoprotective effect of UDCA, (C) 1999 Academic Press.
引用
收藏
页码:537 / 542
页数:6
相关论文
共 39 条
[1]   Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes [J].
Beuers, U ;
Throckmorton, DC ;
Anderson, MS ;
Isales, CM ;
Thasler, W ;
KullakUblick, GA ;
Sauter, G ;
Koebe, HG ;
Paumgartner, G ;
Boyer, JL .
GASTROENTEROLOGY, 1996, 110 (05) :1553-1563
[2]   URSODEOXYCHOLIC ACID FOR TREATMENT OF PRIMARY SCLEROSING CHOLANGITIS - A PLACEBO-CONTROLLED TRIAL [J].
BEUERS, U ;
SPENGLER, U ;
KRUIS, W ;
AYDEMIR, U ;
WIEBECKE, B ;
HELDWEIN, W ;
WEINZIERL, M ;
PAPE, GR ;
SAUERBRUCH, T ;
PAUMGARTNER, G .
HEPATOLOGY, 1992, 16 (03) :707-714
[3]  
BOTLA R, 1995, J PHARMACOL EXP THER, V272, P930
[4]   URSODEOXYCHOLATE MOBILIZES INTRACELLULAR CA-2+ AND ACTIVATES PHOSPHORYLASE-A IN ISOLATED HEPATOCYTES [J].
BOUSCAREL, B ;
FROMM, H ;
NUSSBAUM, R .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (02) :G243-G251
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]   BIOCHEMISTRY OF OXYGEN-TOXICITY [J].
CADENAS, E .
ANNUAL REVIEW OF BIOCHEMISTRY, 1989, 58 :79-110
[7]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[8]   PRESERVATION AND REPERFUSION INJURIES IN LIVER ALLOGRAFTS - AN OVERVIEW AND SYNTHESIS OF CURRENT STUDIES [J].
CLAVIEN, PA ;
HARVEY, PRC ;
STRASBERG, SM .
TRANSPLANTATION, 1992, 53 (05) :957-978
[9]   TISSUE SULFHYDRYL GROUPS [J].
ELLMAN, GL .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1959, 82 (01) :70-77
[10]  
FREEMAN BA, 1982, LAB INVEST, V47, P412