Morrow J D, Chen Y, Brame C J, Yang J, Sanchez S C, Xu J, Zackert W E, Awad J A, Roberts L J
Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA.
Drug Metab Rev. 1999 Feb;31(1):117-39. doi: 10.1081/dmr-100101910.
The discovery of IsoPs as products of nonenzymatic lipid peroxidation has opened up new areas of investigation regarding the role of free radicals in human physiology and pathophysiology. The quantification of IsoPs as markers of oxidative stress status appears to be an important advance in our ability to explore the role of free radicals in the pathogenesis of human disease. An important need in the field of free-radical medicine is information regarding the clinical pharmacology of antioxidant agents. Because of the evidence implicating free radicals in the pathogenesis of a number of human diseases, large clinical trials are planned or underway to assess whether antioxidants can either prevent the development or ameliorate the pathology of certain human disorders. However, data regarding the most effective doses and combination of antioxidant agents to use in these clinical trials is lacking. As mentioned previously, administration of antioxidants suppresses the formation of IsoPs, even in normal individuals. Thus, measurement of IsoPs may provide a valuable approach to define the clinical pharmacology of antioxidants. In addition to being markers of oxidative stress, several IsoPs possess potent biological activity. The availability of additional IsoPs in synthetic form should broaden our knowledge concerning the role of these molecules as mediators of oxidant stress. Despite the fact that considerable information has been obtained since the initial report of the discovery of IsoPs [6], much remains to be understood about these molecules. With continued research in this area, we believe that much new information will emerge that will open up additional important new areas for future investigation.
异前列腺素（IsoPs）作为非酶促脂质过氧化产物的发现，开启了关于自由基在人类生理和病理生理学中作用的新研究领域。将IsoPs作为氧化应激状态标志物进行定量，似乎是我们探索自由基在人类疾病发病机制中作用能力的一项重要进展。自由基医学领域的一个重要需求是有关抗氧化剂临床药理学的信息。由于有证据表明自由基与多种人类疾病的发病机制有关，因此正在计划或正在进行大型临床试验，以评估抗氧化剂是否可以预防某些人类疾病的发生或改善其病理状况。然而，缺乏关于这些临床试验中使用的抗氧化剂最有效剂量和组合的数据。如前所述，即使在正常个体中，给予抗氧化剂也会抑制IsoPs的形成。因此，IsoPs的测量可能为确定抗氧化剂的临床药理学提供一种有价值的方法。除了作为氧化应激的标志物外，几种IsoPs还具有强大的生物活性。以合成形式提供更多的IsoPs应该会拓宽我们对这些分子作为氧化应激介质作用的认识。尽管自IsoPs发现的最初报告[6]以来已经获得了大量信息，但关于这些分子仍有许多有待了解。随着该领域研究的不断深入，我们相信将会出现许多新信息，为未来的研究开辟更多重要的新领域。
