Curcumin protects against acute liver damage in the rat by inhibiting NF-κB, proinflammatory cytokines production and oxidative stress
Curcumin protects against acute liver damage in the rat by inhibiting NF-κB, proinflammatory cytokines production and oxidative stress
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DOI：
10.1016/j.bbagen.2007.02.004
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发表时间：
2007-06-01
影响因子：
3
通讯作者：
Muriel, Pablo
中科院分区：
文献类型：
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作者：
Reyes-Gordillo, Karina;Segovia, Jose;Muriel, Pablo
姜黄素是一种抗炎和抗氧化化合物，其抑制急性四氯化碳诱导的肝损伤的能力被评估。CCl4(4g/kg，P.O.)灌胃造成小鼠急性肝毒性。咖喱素组(200 mg/kg，P.O.)在CCl4给药前和给药后2小时给药。CCl4中毒后，坏死指标(丙氨酸氨基转移酶)和胆汁淤积指标(γ-谷氨酰转肽酶和胆红素)显著升高，但姜黄素治疗可阻止这些影响。作为氧化应激的指标，CCl4使GSH氧化，GSH/GSSG比值显著降低，但被姜黄素维持在正常范围内。除了抗氧化剂特性外，姜黄素还能够阻止核因子-kappaB的激活，从而阻止促炎细胞因子的分泌。因此，在本研究中，我们测定了肿瘤坏死因子-α(TNF-α)、白介素1-β(IL-1β)和白介素6(IL-6)mRNA的浓度以及核因子-kappaB的激活情况。给予CCl4的大鼠表现出显著增加的TNF-α、IL-10和IL-6的产生，而姜黄素显著抑制了这些肝脏损伤中的炎症介质。通过Western Blot分析检测肿瘤坏死因子-α和IL-1β蛋白的产生，证实了这些结果。相应地，这些蛋白被CCl4增加，而这种作用被姜黄素取消。CCl_4可诱导核转录因子-kappaB向核内移位，姜黄素可阻断CCl_4诱导的核转录因子-kappaB DNA结合活性。这些发现表明，姜黄素至少通过两种机制预防急性肝损伤：作为抗氧化剂和抑制核因子-kappaB的激活，从而抑制促炎细胞因子的产生。(C)2007 Elsevier B.V.保留所有权利。
Curcumin, an anti-inflammatory and antioxidant compound, was evaluated for its ability to suppress acute carbon tetrachloride-induced liver damage. Acute hepatotoxicity was induced by oral administration of CCl4 (4 g/kg, p.o.). Curcurnin treatment (200 mg/kg, p.o.) was given before and 2 h after CCl4 administration. Indicators of necrosis (alanine aminotransferase) and cholestasis (gamma-glutamyl transpeptidase and bilirubins) resulted in significant increases after CCl4 intoxication, but these effects were prevented by curcumin treatment. As an indicator of oxidative stress, GSH was oxidized and the GSH/GSSG ratio decreased significantly by CCl4, but was preserved within normal values by curcumin. In addition to its antioxidants properties, curcumin is capable of preventing NF-kappa B activation and therefore to prevent the secretion of proinflammatory cytokines. Therefore, in this study we determined the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) mRNA, and NF-kappa B activation. CCl4-administered rats depicted significant increases in TNF-alpha, IL-10, and IL-6 production, while curcumin remarkably suppressed these mediators of inflammation in liver damage. These results were confirmed by measuring TNF-alpha, and IL-1 beta protein production using Western Blot analysis. Accordingly, these proteins were increased by CCl4 and this effect was abolished by curcumin. Administration of CCl4 induced the translocation of NF-kappa B to the nucleus; CCl4 induced NF-kappa B DNA binding activity was blocked by curcumin treatment. These findings suggest that curcumin prevents acute liver damage by at least two mechanisms: acting as an antioxidant and by inhibiting NF-kappa B activation and thus production of proinflammatory cytokines. (c) 2007 Elsevier B.V. All rights reserved.