Upregulation of heme oxygenase-1 with hemin prevents D-galactosamine and lipopolysaccharide-induced acute hepatic injury in rats

被引：70

作者：

Wen, Tao ^{[1
]}

Wu, Zhi-Ming

Liu, Yan

Tan, Yu-Fen

Rena, Feng

Wu, Hao

机构：

[1] Capital Univ Med Sci, Beijing You An Hosp, Inst Liver Dis, Beijing 100069, Peoples R China

[2] Capital Univ Med Sci, Beijing You An Hosp, Dept Infect Dis, Beijing 100069, Peoples R China

来源：

TOXICOLOGY | 2007年 / 237卷 / 1-3期

关键词：

heme oxygenase-1 (HO-1); liver injury; D-galactosamine (GalN); hemin; tumor necrosis factor-alpha (TNF-alpha); caspase-3;

D O I：

10.1016/j.tox.2007.05.014

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, has been shown to be induced during oxidative injury, and its induction acts as an important cellular defense mechanism against such injuries. In this study, we examined the functional roles of HO-1 induction in a rat model of D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced liver injury. We found that GalN/LPS treatment of rats produced severe hepatic injury, whereas upregulation of HO-1 by hemin pretreatment prevented rats from liver damage, as evidenced by decreased serum ALT, AST levels and ameliorated histological signs in the liver. Induction of HO-1 resulted in a significant decrease in hepatic malondialdehyde (MDA) contents, tumor necrosis factor-alpha. (TNF-alpha) levels, iNOS/NO production, as well as the levels of caspase-3. In contrast, inhibition of HO activity by zinc protoporphyrin-9 (ZnPP, a specific inhibitor of HO) completely reversed HO-1-induced hepatoprotective effect. These data therefore suggested that HO-1 induction provided critical protection against GalN/LPS-induced liver injury, and the protection seemed to be mediated through the anti-oxidant, anti-inflammatory and anti-apoptotic functions. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

引用

页码：184 / 193

页数：10

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