Effects of Kupffer cell blockade on the hepatic expression of metallothionein and heme oxygenase genes in endotoxemic rats with obstructive jaundice

被引:9
作者
Abraham, Szabolcs [1 ]
Hermesz, Edit [2 ]
Szabo, Andrea [3 ]
Ferencz, Agnes [2 ]
Jancso, Zsanett [2 ]
Duda, Erno [4 ]
Abraham, Magdolna [2 ]
Lazar, Gyorgy [5 ]
Lazar, Gyorgy, Jr. [1 ]
机构
[1] Univ Szeged, Dept Surg, H-6720 Szeged, Hungary
[2] Univ Szeged, Dept Biochem & Mol Biol, H-6720 Szeged, Hungary
[3] Univ Szeged, Inst Surg Res, H-6720 Szeged, Hungary
[4] Univ Szeged, Dept Med Biol, H-6720 Szeged, Hungary
[5] Univ Szeged, Inst Pathophysiol, H-6720 Szeged, Hungary
关键词
Gadolinium chloride; Bile duct ligation; Sepsis; Lipopolysaccharide; MESSENGER-RNA ACCUMULATION; NECROSIS-FACTOR-ALPHA; BILE-DUCT LIGATION; GADOLINIUM CHLORIDE; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; MOUSE-LIVER; EXPERIMENTAL CHOLESTASIS; INDUCTION; INJURY;
D O I
10.1016/j.lfs.2011.10.021
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aims: Heme oxygenase (HO) and metallothionein (MT) genes are rapidly upregulated in the liver by pro-inflammatory cytokines and/or endotoxin as protection against cellular stress and inflammation. Gadolinium chloride (GdCl3)-induced Kupffer cell blockade has beneficial consequences in endotoxemia following bile duct ligation. Herein we further characterized the effects of Kupffer cell inhibition on the activation of the antioxidant defense system (HO and MT gene expressions, and antioxidant enzyme activities) in response to endotoxemia and obstructive jaundice. Main methods: The isoform-specific expression of MT and HO genes was assessed (RT-PCR) in rat livers following 3-day bile duct ligation, 2-h lipopolysaccharide treatment (1 mg/kg) or their combination, with or without GdCl3 pretreatment (10 mg/kg, 24 h before endotoxin). Lipid peroxidation, DNA damage and hepatic antioxidant enzyme activities were also assessed. Key findings: All these challenges induced similar extents of DNA damage, whereas the lipid peroxidation increased only when endotoxemia was combined with biliary obstruction. The MT and HO mRNA levels displayed isoform-specific changes: those of MT-1 and HO-2 did not change appreciably, whereas those of MT-2 and HO-1 increased significantly in 2-h endotoxemia, with or without obstructive jaundice. Among the enzymes reflecting the endogenous protective mechanisms, the catalase and copper/zinc-superoxide dismutase levels decreased, while that of Mn-SOD slightly increased. Interestingly, GdCl3 alone induced lipid peroxidation, DNA damage and MT-2 expression. In response to GdCl3, HO-1 induction was significantly lower in each model. Significance: Despite its moderate hepatocellular toxicity, the ameliorated stress-induced hepatic reactions provided by GdCl3 may contribute to its protective effects. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:140 / 146
页数:7
相关论文
共 56 条
  • [1] Abe S, 1987, Experientia Suppl, V52, P587
  • [2] Kupffer cell blockade improves the endotoxin-induced microcirculatory inflammatory response in obstructive jaundice
    Abraham, Szabolcs
    Szabo, Andrea
    Kaszaki, Jozsef
    Varga, Renata
    Eder, Katalin
    Duda, Erno
    Lazar, Gyoergy
    Tiszlavicz, Laszlo
    Boros, Mihaly
    Lazar, Gyoergy, Jr.
    [J]. SHOCK, 2008, 30 (01): : 69 - 74
  • [3] How many transcription factors does it take to turn on the heme oxygenase-1 gene?
    Alam, Jawed
    Cook, Julia L.
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2007, 36 (02) : 166 - 174
  • [4] Depletion of Kupffer cell function by gadolinium chloride attenuates thioacetamide-induced hepatotoxicity -: Expression of metallothionein and HSP70
    Andrés, D
    Sánchez-Reus, I
    Bautista, M
    Cascales, M
    [J]. BIOCHEMICAL PHARMACOLOGY, 2003, 66 (06) : 917 - 926
  • [5] Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver
    Bauer, I
    Wanner, GA
    Rensing, H
    Alte, G
    Miescher, EA
    Wolf, B
    Pannen, BHJ
    Clemens, MG
    Bauer, M
    [J]. HEPATOLOGY, 1998, 27 (03) : 829 - 838
  • [6] SUPEROXIDE DISMUTASE - IMPROVED ASSAYS AND AN ASSAY APPLICABLE TO ACRYLAMIDE GELS
    BEAUCHAM.C
    FRIDOVIC.I
    [J]. ANALYTICAL BIOCHEMISTRY, 1971, 44 (01) : 276 - &
  • [7] BEERS RF, 1952, J BIOL CHEM, V195, P133
  • [8] Effect of surgically induced cholestasis on the levels of hepatic zinc and metallothionein in rat liver
    Brambilla, E
    Munoz-Sanchez, JL
    Waalkes, MP
    Albores, A
    [J]. BIOLOGICAL TRACE ELEMENT RESEARCH, 2000, 78 (1-3) : 255 - 264
  • [9] INTERLEUKIN-6 RELEASE BY RAT-LIVER MACROPHAGES
    BUSAM, KJ
    BAUER, TM
    BAUER, J
    GEROK, W
    DECKER, K
    [J]. JOURNAL OF HEPATOLOGY, 1990, 11 (03) : 367 - 373
  • [10] Camhi S L, 1995, New Horiz, V3, P170