The generation and actions of isoprostanes

The discovery of IsoPs as unique products of non-enzymatic lipid peroxidation has been fortuitous in a many ways and has opened up numerous new avenues for investigation. First, the use of quantification of IsoPs as markers of oxidative stress status in vivo appears to be a major advance in our ability to explore the role of free radicals in the pathogenesis of human disease. One drawback related to this is the current lack of more facile and less expensive methods than mass spectrometry for the measurement of IsoPs. This greatly hampers the general use of measuring IsoPs by investigators in the free radical field. However, efforts are underway both in academia and industry to develop specific and reliable immunoassay methods for measurement of IsoPs. This most likely will lead to a prolific expansion of the use of measurements of IsoPs to assess oxidative stress status in vivo both in animal models of oxidative injury and in humans. Another great 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, e.g. atherosclerosis, 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 that accurately informs us regarding the most effective doses and combination of antioxidant agents to use in these clinical trials is lacking. As mentioned previously, administration of antioxidants can be shown to suppress the formation of IsoPs, even in normal individuals. Thus, measurement of IsoPs should provide a valuable approach to define the clinical pharmacology of antioxidants. In addition to being valuable markers of oxidative stress, the IsoPs tested thus far possess interesting and potent biological activity. In this regard, the availability of additional IsoPs in synthetic form should significantly broaden our knowledge concerning the role of these molecules as mediators of oxidant stress. In addition, information regarding the nature of the receptor(s) that mediate the biological actions of IsoPs will be of considerable importance as it contributes to the development of specific antagonists or agonists of the biological actions of IsoPs. Although considerable information has been obtained since the initial report of the discovery of IsoPs in 1990 [5,7], much remains to be understood about these unique molecules. With continued research in this area, we are confident that much new valuable information will be forthcoming which, in turn, will also likely open up additional important new areas for future investigation.