Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators:: protectin D1 and 17S-hydroxy-DHA
Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators:: protectin D1 and 17S-hydroxy-DHA
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DOI：
10.1096/fj.06-6250fje
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发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Claria, Joan
中科院分区：
文献类型：
--
作者：
Gonzalez-Periz, Ana;Planaguma, Anna;Claria, Joan
二十二碳六烯酸（DHA）是一种欧米伽-3必需脂肪酸，可降低许多疾病的发病率和严重程度。最近，一个新的系列DHA衍生的脂质介质具有强大的保护作用已被确定。在这项研究中，我们证明了这些DHA衍生产品的饮食放大保护肝脏免受坏死性炎症损伤。在体外，补充DHA的肝细胞显着减少过氧化氢诱导的DNA损伤，通过“彗星试验”和氧化应激，通过测量丙二醛水平的评估。在体内，膳食补充DHA的小鼠改善四氯化碳诱导的坏死性炎症损伤。此外，在喂食富含DHA饮食的小鼠中，肝脏环氧合酶-2表达和PGE（2）水平显著降低。在这些动物中，DHA衍生的脂质介质（即，采用高效液相色谱-气相色谱/质谱联用技术检测17 S-羟基DHA（17 S-HDHA）和保护素D1。与这些发现一致，合成的17-HDHA消除了肝细胞中的遗传毒性和氧化损伤，并降低了巨噬细胞中TNF-α的释放和5-脂氧合酶的表达。在反式激活试验中，17-HDHA以浓度依赖性方式作为PPAR γ激动剂。总之，这些发现确定了DHA衍生产品，特别是17 S-HDHA和保护素D1在介导膳食DHA对坏死性肝损伤的保护作用方面的潜在作用。Gonzalez-Periz，A.，Planaguma，A.，Gronert，K.，米克尔河，洛佩斯-帕拉，M.，Titos，E.，霍里略河Ferre，N.，德乌洛费乌河阿罗约，五，Rodes，J.，Claria，J.二十二碳六烯酸（DHA）通过转化为保护性脂质介质：保护素D1和17 S-hydroxyDHA来减轻肝损伤。
Docosahexaenoic acid (DHA) is a omega-3 essential fatty acid that reduces the incidence and severity of a number of diseases. Recently, a novel series of DHA-derived lipid mediators with potent protective actions has been identified. In this study we demonstrate that dietary amplification of these DHA-derived products protects the liver from necroinflammatory injury. In vitro, supplementation of hepatocytes with DHA significantly reduced hydrogen peroxide-induced DNA damage, evaluated by the "comet assay," and oxidative stress, determined by measurement of malondialdehyde levels. In vivo, dietary supplementation of mice with DHA ameliorated carbon tetrachloride-induced necroinflammatory damage. In addition, hepatic cyclooxygenase-2 expression and PGE(2) levels were significantly reduced in mice fed DHA-enriched diets. In these animals, increased hepatic formation of DHA-derived lipid mediators (i.e., 17S-hydroxy- DHA (17S-HDHA) and protectin D1) was detected by HPLC-gas chromatography/mass spectrometry analysis. Consistent with these findings, synthetic 17-HDHA abrogated genotoxic and oxidative damage in hepatocytes and decreased TNF-alpha release and 5-lipoxygenase expression in macrophages. In a transactivation assay, 17-HDHA acted in a concentration-dependent manner as a PPAR gamma agonist. Taken together, these findings identify a potential role for DHA-derived products, specifically 17S-HDHA and protectin D1, in mediating the protective effects of dietary DHA in necroinflammatory liver injury.-Gonzalez-Periz, A., Planaguma, A., Gronert, K., Miquel, R., Lopez- Parra, M., Titos, E., Horrillo, R., Ferre, N., Deulofeu, R., Arroyo, V., Rodes, J., Claria, J. Docosahexaenoic acid ( DHA) blunts liver injury by conversion to protective lipid mediators: protectin D1 and 17S-hydroxyDHA.