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

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1999年 / 263卷 / 02期

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

页码：537 / 542

页数：6

共 39 条

[21] SUPEROXIDE GENERATION BY NADPH-CYTOCHROME-P-450 REDUCTASE - THE EFFECT OF IRON CHELATORS AND THE ROLE OF SUPEROXIDE IN MICROSOMAL LIPID-PEROXIDATION [J].

MOREHOUSE, LA ;

THOMAS, CE ;

AUST, SD .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1984, 232 (01) :366-377

[22] Redox regulation of cellular activation [J].

Nakamura, H ;

Nakamura, K ;

Yodoi, J .

ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :351-369

[23] QUANTIFICATION OF MESSENGER-RNA BY NONRADIOACTIVE RT-PCR AND CCD IMAGING-SYSTEM [J].

NAKAYAMA, H ;

YOKOI, H ;

FUJITA, J .

NUCLEIC ACIDS RESEARCH, 1992, 20 (18) :4939-4939

[24] THE MAP KINASE CASCADE IS ESSENTIAL FOR DIVERSE SIGNAL TRANSDUCTION PATHWAYS [J].

NISHIDA, E ;

GOTOH, Y .

TRENDS IN BIOCHEMICAL SCIENCES, 1993, 18 (04) :128-131

[25] OXIDATION OF ASCORBIC-ACID WITH SUPEROXIDE ANION GENERATED BY XANTHINE XANTHINE OXIDASE SYSTEM [J].

NISHIKIMI, M .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1975, 63 (02) :463-468

[26] Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis [J].

Poupon, RE ;

Lindor, KD ;

CauchDudek, K ;

Dickson, ER ;

Poupon, R ;

Heathcote, EJ .

GASTROENTEROLOGY, 1997, 113 (03) :884-890

[27] USE OF LACTATE-DEHYDROGENASE RELEASE TO ASSESS CHANGES IN CULTURE VIABILITY [J].

RACHER, AJ ;

LOOBY, D ;

GRIFFITHS, JB .

CYTOTECHNOLOGY, 1990, 3 (03) :301-307

[28] URSODEOXYCHOLIC ACID CHOLERESIS - RELATIONSHIP TO BILIARY HCO3- AND EFFECTS OF NA+-H+ EXCHANGE INHIBITORS [J].

RENNER, EL ;

LAKE, JR ;

CRAGOE, EJ ;

VANDYKE, RW ;

SCHARSCHMIDT, BF .

AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 254 (02) :G232-G241

[29] LIVER-CELL NECROSIS - CELLULAR MECHANISMS AND CLINICAL IMPLICATIONS [J].

ROSSER, BG ;

GORES, GJ .

GASTROENTEROLOGY, 1995, 108 (01) :252-275

[30]

RUGSTAD HE, 1977, BIOCHEM PHARMACOL, V27, P647

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