Measurement of F2-isoprostanes as an index of oxidative stress in vivo

Measurement of F2-isoprostanes as an index of oxidative stress in vivo
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DOI:
10.1016/s0891-5849(99)00264-6
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发表时间:
2000-02-15
影响因子:
7.4
通讯作者:
Morrow, JD
Morrow, JD
中科院分区:
医学1区
文献类型:
--
作者:
Roberts, LJ;Morrow, JD

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在1990年,我们发现了前列腺素F-2样化合物,F-2-异前列腺素(F-2-IsoPs),在体内的花生四烯酸的非酶自由基诱导的过氧化反应的形成。F-2-IsoP最初形成为与磷脂酯化,然后以游离形式释放。有几个有利的属性使得F-2-IsoPs的测量作为体内氧化应激的可靠指标具有吸引力:(i)F-2-IsoPs是脂质过氧化的特异性产物;(ii)它们是稳定的化合物;(iii)水平以可检测的量存在于所有正常生物体液和组织中,允许定义正常范围;(iv)在许多氧化损伤的动物模型中,它们的形成在体内显著增加;(v)它们的形成受抗氧化状态调节;和(vi)它们的水平不受饮食中脂质含量的影响。血浆中F-2-IsoPs的测量可用于评估F-2-IsoPs的总内源性产生,而磷脂中酯化水平的测量可用于确定目标靶位点中脂质过氧化的程度。最近,我们开发了一种测定尿中F-2-IsoPs代谢产物的方法,该方法为大型临床研究中评估F-2-IsoPs的总内源性产生提供了一种有价值的非侵入性综合方法。(C)2000 Elsevier Science Inc.
In 1990 we discovered the formation of prostaglandin F-2-like compounds, F-2-isoprostanes (F-2-IsoPs), in vivo by nonenzymatic free radical-induced peroxidation of arachidonic acid. F-2-IsoPs are initially formed esterified to phospholipids and then released in free form. There are several favorable attributes that make measurement of F-2-IsoPs attractive as a reliable indicator of oxidative stress in vivo: (i) F-2-IsoPs are specific products of Lipid peroxidation; (ii) they are stable compounds; (iii) levels are present in detectable quantities in all normal biological fluids and tissues, allowing the definition of a normal range; (iv) their formation increases dramatically in vivo in a number of animal models of oxidant injury; (v) their formation is modulated by antioxidant status; and (vi) their levels are not effected by lipid content of the diet. Measurement of F-2-IsoPs in plasma can be utilized to assess total endogenous production of F-2-IsoPs whereas measurement of levels esterified in phospholipids can be used to determine the extent of lipid peroxidation in target sites of interest. Recently, we developed an assay for a urinary metabolite of F-2-IsoPs, which should provide a valuable noninvasive integrated approach to assess total endogenous production of F-2-IsoPs in large clinical studies. (C) 2000 Elsevier Science Inc.