Novel eicosanoids. Isoprostanes and related compounds.
The discovery of IsoPs has been an interesting development for a number of reasons, apart from the fact that it involves novel biochemistry. The simple fact that prostanoids are produced nonenzymatically in prodigous quantities in vivo and in much greater quantities than prostaglandins generated by the cyclooxygenase enzyme was a remarkable finding. The observation that detectable quantities of F2-IsoPs are present in all tissues and human biological fluids carries interesting implications. Previously, there had been little convincing evidence for the occurrence of lipid peroxidation in vivo except under unusual conditions of severe oxidative stress. However, the finding that F2-IsoPs can be easily detected in normal humans suggests a continuous level of ongoing oxidative injury that is not completely suppressed by the elaborate system of antioxidant defenses that have evolved. Another very important aspect of the discovery of IsoPs is that it has brought to the field a long sought after reliable approach to assess oxidative stress status in vivo. The continuing and expanded use of measurements of IsoPs for this purpose will contribute in a very valuable way to advancing our understanding of the role of free radicals in human disease processes. Further, the finding that these compounds are not simply markers of oxidant injury but can also exert potent biological actions both by interaction with specific receptors and, in the case of IsoLGs and cyclopentenenone IsoPs, by virtue of their chemical reactivity, has identified several new classes of molecules that are produced by free radical-induced lipid peroxidation that may mediate some of the adverse sequela of oxidant injury. The elucidation of the variety of compounds that are produced as products of the IsoP pathway and more recently the NP pathway provides vast new areas for scientific inquiry that should yield new and interesting information as this area continues to advance.
Roberts
L J
LJ
Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
Brame
C J
CJ
Chen
Y
Y
Morrow
J D
JD
D000975:Antioxidants / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D015227:Lipid Peroxidation; D009420:Nervous System / Q000378:metabolism; D018384:Oxidative Stress; D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins / Q000378:metabolism*
D000975:Antioxidants; D015777:Eicosanoids; D005227:Fatty Acids; D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid