Sethi Sanjeev
Department of Pathology, 5243 RCP, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA.
Redox Rep. 2002;7(6):369-78. doi: 10.1179/135100002125001144.
Omega-3 fatty acids which are abundant in fish oil improve the prognosis of several chronic inflammatory diseases that are characterized by leukocyte-mediated tissue injury. The omega-3 fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. Our data suggest that the beneficial effects of fish oil may be due to the oxidative modification of omega-3 fatty acids. The oxidized products inhibit leukocyte adhesion receptor expression and leukocyte-endothelial interactions. Oxidized EPA is a potent inhibitor of leukocyte interactions with the endothelium compared to native EPA, both in vitro and in an in vivo context of inflammation. The effects of oxidized EPA are mediated through activation of PPARalpha and subsequent inhibition of NF-kappaB, leading to the down-regulation of leukocyte adhesion receptor expression required for leukocyte-endothelial interactions. We propose that oxidation of EPA and its activation of PPARalpha and subsequent inhibition of NF-kappaB is the underlying mechanism for the beneficial effects of fish oil.
鱼油中富含的ω-3脂肪酸可改善几种以白细胞介导的组织损伤为特征的慢性炎症性疾病的预后。ω-3脂肪酸，如二十碳五烯酸（EPA），高度多不饱和且易于氧化。我们的数据表明，鱼油的有益作用可能归因于ω-3脂肪酸的氧化修饰。氧化产物可抑制白细胞黏附受体表达和白细胞-内皮细胞相互作用。与天然EPA相比，氧化型EPA在体外和体内炎症环境中都是白细胞与内皮细胞相互作用的有效抑制剂。氧化型EPA的作用是通过激活PPARα并随后抑制NF-κB介导的，导致白细胞-内皮细胞相互作用所需的白细胞黏附受体表达下调。我们提出，EPA的氧化及其对PPARα的激活以及随后对NF-κB的抑制是鱼油产生有益作用的潜在机制。
