Novel Eicosanoids: Isoprostanes and Related Compounds L. Jackson Roberts, II, Cynthia J. Brame, Yan Chen,

Abstract

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.

Interaction of Ascorbate and α-Tocopherol in Resealed Human Erythrocyte Ghosts

“…F 2 -isoprostanes are derived from free radical-mediated oxidation of arachidonic acid and have been shown to provide specific and extremely sensitive estimates of lipid peroxidation, both in vivo (39) and in vitro (40). In contrast to lipid hydroperoxides, F 2 -isoprostanes are chemically stable end products that can remain esterified in tissues or be released by the actions of phospholipases (36). Ghosts resealed in the presence or absence of ascorbate had low levels of F 2 -isoprostanes, and ferricyanide treatment more than doubled F 2 -isoprostane formation (Table I).…”

“…F 2 -isoprostanes were extracted from ghost membranes, purified by TLC, derivatized, separated by selected ion monitoring gas chromatography, and quantified by a gas chromatography/mass spectrometric assay employing stable isotope dilution techniques, as described previously (36). Lipid hydroperoxides in liposomes and erythrocyte ghosts were measured using the FOX2 assay (34).…”

Accelerated telomere shortening in response to life stress

“…Vitamin E (alpha-tocopherol) was measured with HPLC from serum isolated from a blood sample protected by foil (ARUP Laboratories, Salt Lake City). F 2 -isoprostanes level, a reliable measure of oxidative stress, was quantified from a 12-hour nocturnal urine sample from a subsample of 44 of the women (urine was not collected on the first 14 subjects) by using a highly accurate and precise gas chromatographic͞mass spectrometric assay (16) and adjusting for creatinine levels. An index of oxidative stress was calculated as the ratio of (isoprostanes per milligram of creatinine)͞vitamin E. This index represents the net oxidative stress effect, taking into account one marker of oxidative stress and of antioxidant defenses.…”

A Causative Role for Redox Cycling of Myoglobin and Its Inhibition by Alkalinization in the Pathogenesis and Treatment of Rhabdomyolysis-induced Renal Failure

“…Extraction and Measurement of F 2 -IsoPs-Esterified F 2 -IsoPs in LDL and kidney and free F 2 -IsoPs in urine were extracted and quantified by stable isotope dilution mass spectrometric assay as described, except [ 2 H 4 ]8-iso-prostaglandin F 2␣ (Cayman Chemical Co., Ann Arbor, MI) was used as the internal standard (34). Urinary excretion of F 2 -IsoPs was normalized to creatinine clearance to correct for the widely differing degrees of renal function, i.e.…”