Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress

被引：113

作者：

Wang, H ^{[1
]}

Wei, W ^{[1
]}

Wang, NP ^{[1
]}

Gui, SY ^{[1
]}

Wu, L ^{[1
]}

Sun, WY ^{[1
]}

Xu, SY ^{[1
]}

机构：

[1] Anhui Med Univ, Inst Clin Pharmacol, Hefei 230032, Peoples R China

来源：

LIFE SCIENCES | 2005年 / 77卷 / 15期

关键词：

melatonin; liver fibrosis; oxidative stress;

D O I：

10.1016/j.lfs.2005.04.013

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：

Melatonin is reported to exhibit a wide variety of biological effects, including antioxidant and anti-inflammatory. Evidence shows the important role of oxidative stress in the etiopathogenesis of hepatic fibrosis. The aim of this study was to investigate the protective effects of administration of melatonin in rats with carbon tetrachloride-induced fibrosis for 6 weeks. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examinations. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) levels were evaluated in tissue homogenates by spectrophotometry. The nuclear factor-kappaB (NF-kappa B) in liver tissue was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) concentrations in Kupffer cells (KCs) culture supernatants were measured with ELISA. The rats injected subcutaneously with CCl4 for 6 weeks resulted in hepatic fibrotic changes increased hydroxyproline and MDA levels, and decreased GSH-px and SOD levels, whereas melatonin reversed these effects. Furthermore, melatonin inhibited the expression of NF-kappa B in liver tissue and decreasing production of proinflammatory cytokines such as TNF-alpha and IL-1 beta from KCs in fibrotic rats. These present results suggest that melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress and proinflammatory cytokines production. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：1902 / 1915

页数：14

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