Pioglitazone prevents early-phase hepatic fibrogenesis caused by carbon tetrachloride

被引:117
作者
Kon, K [1 ]
Ikejima, K [1 ]
Hirose, M [1 ]
Yoshikawa, M [1 ]
Enomoto, N [1 ]
Kitamura, T [1 ]
Takei, Y [1 ]
Sato, N [1 ]
机构
[1] Juntendo Univ, Sch Med, Dept Gastroenterol, Bunkyo Ku, Tokyo 1138421, Japan
关键词
peroxysome proliferator-activated receptor; (PPAR); thiazolidinedione derivatives; pioglitazone; hepatic fibrogenesis; carbon tetrachloride; hepatic stellate cells; type I collagen; tumor necrosis factor (TNF)-alpha;
D O I
10.1006/bbrc.2002.6385
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
Here we investigated the effect of pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, on early-phase hepatic fibrogenesis in vivo caused by acute carbon tetrachloride (CCl4) administration in the rat. Pioglitazone (1 mg/kg BW) prevented pericentral fibrosis and induction of alpha-smooth muscle actin (SMA) 72 h after CCl4 administration (1 ml/kg BW). CCl4 induction of alpha1(I)procollagen mRNA in the liver was blunted by pioglitazone to the levels almost 2/3 of CCl4 alone. Pioglitazone also prevented CCl4-induced hepatic inflammation and necrosis, as well as increases in serum tumor necrosis factor-alpha levels. Further, pioglitazone inhibited the induction of alphaSMA and type I collagen in primary cultured hepatic stellate cells in a dose-dependent manner. In conclusion, pioglitazone inhibits both hepatic inflammation and activation of hepatic stellate cells, thereby ameliorating early-phase fibrogenesis in the liver following acute CCl4. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:55 / 61
页数:7
相关论文
共 24 条
[1]   THE INVOLVEMENT OF KUPFFER CELLS IN CARBON-TETRACHLORIDE TOXICITY [J].
EDWARDS, MJ ;
KELLER, BJ ;
KAUFFMAN, FC ;
THURMAN, RG .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1993, 119 (02) :275-279
[2]   15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) IS A LIGAND FOR THE ADIPOCYTE DETERMINATION FACTOR PPAR-GAMMA [J].
FORMAN, BM ;
TONTONOZ, P ;
CHEN, J ;
BRUN, RP ;
SPIEGELMAN, BM ;
EVANS, RM .
CELL, 1995, 83 (05) :803-812
[3]  
FRIEDMAN SL, 1993, NEW ENGL J MED, V328, P1828
[4]   Peroxisome proliferator-activated receptor γ transcriptional regulation is involved in platelet-derived growth factor-induced proliferation of human hepatic stellate cells [J].
Galli, A ;
Crabb, D ;
Price, D ;
Ceni, E ;
Salzano, R ;
Surrenti, C ;
Casini, A .
HEPATOLOGY, 2000, 31 (01) :101-108
[5]  
IKEDA H, 1990, ARZNEIMITTEL-FORSCH, V40-1, P156
[6]   Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals [J].
Ikejima, K ;
Honda, H ;
Yoshikawa, M ;
Hirose, M ;
Kitamura, T ;
Takei, Y ;
Sato, N .
HEPATOLOGY, 2001, 34 (02) :288-297
[7]   PPAR-γ agonists inhibit production of monocyte inflammatory cytokines [J].
Jiang, CY ;
Ting, AT ;
Seed, B .
NATURE, 1998, 391 (6662) :82-86
[8]   CARBON TETRACHLORIDE-INDUCED LIPID-PEROXIDATION DEPENDENT ON AN ETHANOL-INDUCIBLE FORM OF RABBIT LIVER MICROSOMAL CYTOCHROME-P-450 [J].
JOHANSSON, I ;
INGELMANSUNDBERG, M .
FEBS LETTERS, 1985, 183 (02) :265-269
[9]   Roles of PPARs in health and disease [J].
Kersten, S ;
Desvergne, B ;
Wahli, W .
NATURE, 2000, 405 (6785) :421-424
[10]  
Kon K, 2001, HEPATOLOGY, V34, p403A