Resveratrol attenuates lipopolysaccharide-induced hepatitis in D-galactosamine sensitized rats: Role of nitric oxide synthase 2 and heme oxygenase-1
Resveratrol attenuates lipopolysaccharide-induced hepatitis in D-galactosamine sensitized rats: Role of nitric oxide synthase 2 and heme oxygenase-1
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DOI：
10.1016/j.niox.2009.09.004
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发表时间：
2009-11-01
影响因子：
3.9
通讯作者：
Zidek, Zdenek
中科院分区：
文献类型：
--
作者：
Farghali, Hassan;Cerny, Dalibor;Zidek, Zdenek
本研究旨在探讨白藜芦醇（RES）预处理对D-氨基半乳糖（D-GalN; 800 mg/kg）增强脂多糖（LPS; 0.5 μ g/kg）诱导的大鼠肝衰竭作用的影响。通过测定血浆丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、α-谷胱甘肽S-转移酶（α-GST）和胆红素（BILI）来评估肝功能。采用NO2-/NO3-比色法测定血浆NO2-。在血浆和肝匀浆中估计非酶和酶抗氧化剂（谷胱甘肽和过氧化氢酶）。通过硫代巴比妥酸反应物质（TEARS）和共轭二烯（CD）评价脂质过氧化。采用光学显微镜和电子显微镜进行形态学检查。采用实时荧光定量逆转录PCR（RT-PCR）技术，观察肝组织中诱导型一氧化氮合酶（NOS-2）/一氧化氮（NO）和诱导型血红素加氧酶（HO-1）在暴发性肝衰竭中的药理学作用及白藜芦醇的调节作用。在本研究中，我们发现，在LPS/D-GaIN肝毒性模型中，白藜芦醇的肝保护作用的机制包括NO的减少、NOS-2的下调、氧化应激参数的改变和HO-1的调节，这导致肝损伤后肝毒性标志物和形态学的总体改善。(C)2009 Elsevier Inc. All rights reserved.
The goal of study was directed to investigate the effects of resveratrol (RES) pretreatment on the enhancing action of D-galactosamine (D-GalN; 800 mg/kg) on lipopolysaccharide (LPS; 0.5 mu g/kg) inducing liver failure in rats. Liver function was assessed by determination of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-glutathione S-transferase (alpha GST) and bilirubin (BILI). Plasma NO2- was assessed by NO2-/NO3- colorimetric kit. The estimation of nonenzymatic and enzymatic antioxidants (glutathione and catalase) was performed in plasma and liver homogenate. Lipid peroxidation was evaluated by the thiobarbituric acid reacting substances (TEARS) and the conjugated dienes (CD). Morphological examinations using light and electron microscopy were performed. Observations related to pharmacological increases of inducible nitric oxide synthase (NOS-2)/nitric oxide (NO) and inducible heme oxygenase (HO-1) in fulminant hepatic failure and modulation by resveratrol were followed up by real-time reverse transcription PCR (RT-PCR) in liver tissue. In the present study we found that among the mechanisms responsible for the hepatoprotective effect of resveratrol in the LPS/D-GaIN liver toxicity model are reduction in NO, downregulation of NOS-2, modification of oxidative stress parameters and modulation of HO-1 which led to overall improvement in hepatotoxic markers and morphology after the hepatic insult. (C) 2009 Elsevier Inc. All rights reserved.