Naringenin attenuates CCl4-induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats
Naringenin attenuates CCl4-induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats
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DOI：
10.1111/1440-1681.12230
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发表时间：
2014-06-01
影响因子：
2.9
通讯作者：
Alilou, Mostafa
中科院分区：
文献类型：
--
作者：
Esmaeili, Mohammad Ali;Alilou, Mostafa
研究了柚皮素对四氯化碳（CCl4）诱导大鼠肝损伤的保护作用及其机制。40只大鼠被分为5组。ⅰ组和ⅱ组分别作为正常肝组和损伤肝组；第三组大鼠以标准药物水飞蓟素为阳性对照；IV组、V组（柚皮素处理组）给予柚皮素50mg/kg， p.o.，连用7d。采集肝脏标本，评估mRNA和蛋白表达、组织学变化和氧化应激。柚皮素抑制CCl4诱导的脂质过氧化，降低血清肝酶水平。此外，柚皮素增加了CCl4处理大鼠肝脏还原性谷胱甘肽含量和抗氧化酶活性。柚皮素通过下调ccl4诱导的肿瘤坏死因子(TNF)-、诱导型一氧化氮合酶（iNOS）和环加氧酶（COX-2）的蛋白和mRNA水平，减轻肝脏炎症。柚皮素处理显著提高损伤肝脏中nf - e2相关因子2 （Nrf2）和血红素加氧酶（HO-1）的表达。在CCl4单独处理的大鼠中，核Nrf2表达及其靶基因（如HO-1， NQO1和谷胱甘肽s -转移酶α 3 (GST-a3)）的mRNA水平下降。总之，研究结果表明，柚皮素可以保护肝脏免受氧化应激，可能是通过激活Nrf2的核易位以及减弱TNF-通路，从而在肝组织中引发抗炎反应。
The possible protective effects of naringenin, a naturally occurring citrus flavonone, on carbon tetrachloride (CCl4)-induced liver injury in rats and the mechanism underlying its effects were investigated. Forty rats were divided into five groups. Rats in Groups I and II served as the normal and injured liver groups, respectively; Group III rats were treated with the standard drug silymarin as a positive control; and rats in Groups IV and V (naringenin-treated groups) were administrated 50mg/kg, p.o., naringenin for 7days. Liver samples were collected to evaluate mRNA and protein expression, histological changes and oxidative stress. Naringenin inhibited lipid peroxidation and reduced serum levels of hepatic enzymes induced by CCl4. In addition, naringenin increased the liver content of reduced glutathione and the activity of anti-oxidant enzymes in rats treated with CCl4. Naringenin attenuated liver inflammation by downregulating CCl4-induced activation of tumour necrosis factor (TNF)-, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) at both the protein and mRNA levels. Naringenin treatment significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers. In rats treated with CCl4 alone, decreases were seen in nuclear Nrf2 expression and in the mRNA levels of its target genes (e.g. HO-1, NQO1 and glutathione S-transferase alpha 3 (GST-a3)). Together, the results suggest that naringenin can protect the liver against oxidative stress, presumably by activating the nuclear translocation of Nrf2 as well as attenuating the TNF- pathway to elicit an anti-inflammatory response in liver tissue.