The isoprostanes: unique bioactive products of lipid peroxidation.
The discovery of IsoPs as products of non-enzymatic 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. A drawback related to this, however, has been lack of more facile and less expensive methods than mass spectrometry for the measurement of IsoPs. On the other hand, the recent introduction of immunoassay methods for measurement of IsoPs may alleviate this problem, provided they are specific and reliable. If this is the case, immunoassay methodology will most likely lead to an expansion of the use of measurements of IsoPs to assess oxidative stress status in vivo. Another 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 defining the clinical pharmacology of antioxidants. In addition to being markers of oxidative stress, at least two 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. Moreover, information regarding the nature of the receptor(s) that mediate the biological actions of IsoPs will be of considerable importance to the development of specific antagonists or agonists of the biological actions of IsoPs. Despite the fact that considerable information has been obtained since the initial report of the discovery of IsoPs, 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.
Morrow
J D
JD
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6602, USA.
Roberts
L J
LJ
D015415:Biomarkers; D015237:Dinoprost / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D028441:F2-Isoprostanes; D005609:Free Radicals; D006801:Humans; D007536:Isomerism; D015289:Leukotrienes / Q000378:metabolism; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D011453:Prostaglandins / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism
D015415:Biomarkers; D028441:F2-Isoprostanes; D005609:Free Radicals; D015289:Leukotrienes; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D013931:Thromboxanes; C034671:prostaglandin F2alpha receptor; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost