Isoprostane Explained

The isoprostanes are prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidationof essential fatty acids (primarily arachidonic acid) without the direct action of cyclooxygenase (COX) enzymes. The compounds were discovered in 1990 by L. Jackson Roberts and Jason D. Morrow in the Division of Clinical Pharmacology at Vanderbilt University.^{[1] [2] [3] [4]} These nonclassical eicosanoids possess potent biological activity as inflammatory mediators that augment the perception of pain.^[5] These compounds are accurate markers of lipid peroxidation in both animal and human models of oxidative stress.

Elevated levels of isoprostanes are suspected of contributing to increased risk of heart attack in patients taking Coxibs. Isoprostanes and their metabolites have also been shown to be elevated in the urine of cigarette smokers, and have been suggested as biomarkers of oxidative stress in smokers.^[6]

Abundance

Polyunsaturated fatty acids other than arachidonic acid are also vulnerable to reactive oxygen species and produce isoprostanes. For example, in addition to the four classes of F2-isoprostanes that can arise from arachidonic acid, peroxidation of eicosapentaenoic acid (EPA) is predicted to lead to the generation of six classes of F3 isoprostanes, α-linolenic and γ-linolenic acids to two classes of E1- and F1-isoprostanes, and docosahexaenoic acid to eight classes of D4-isoprostanes and eight classes of E4-isoprostanes. Each of the classes comprise up to eight racemic isomers, leading to an astounding number of isoprostane molecules.^[7]

See also

• Neuroprostanes
• Prostaglandin

References

1. Morrow. JD. Harris TM . Roberts LJ 2nd . Noncyclooxygenase oxidative formation of a series of novel prostaglandins: analytical ramifications for measurement of eicosanoids. Analytical Biochemistry. 1990. 184. 1. 1–10. 2321745. 10.1016/0003-2697(90)90002-q.
2. Morrow. JD. Hill KE . Burk RF . Nammour TM . Badr KF . Roberts LJ 2nd . A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism.. Proceedings of the National Academy of Sciences USA. 1990. 87. 23. 9383–9387 . 10.1073/pnas.87.23.9383. 55169 . 2123555. 1990PNAS...87.9383M. free.
3. COX activity produces H₂O₂ which may non-enzymatically produce isoprostanes.
4. Morrow JD, Roberts LJ . The isoprostanes. Current knowledge and directions for future research . Biochem. Pharmacol. . 51 . 1 . 1–9 . 1996 . 8534261 . 10.1016/0006-2952(95)02072-1.
5. Evans AR, Junger H, Southall MD, etal . Isoprostanes, novel eicosanoids that produce nociception and sensitize rat sensory neurons . J. Pharmacol. Exp. Ther. . 293 . 3 . 912–20 . 2000 . 10869392 .
6. 10.1016/j.freeradbiomed.2011.03.019 . 50 . 12 . 1787–1793 . Seet . Raymond C.S. . Lee . Chung-Yung J. . Loke . Wai Mun . Huang . Shan Hong . Huang . Huiwen . Looi . Woan Foon . Chew . Eng Soh . Quek . Amy M.L. . Lim . Erle C.H. . Halliwell . Barry . Biomarkers of oxidative damage in cigarette smokers: Which biomarkers might reflect acute versus chronic oxidative stress? . . 2011 . 21420490 . 8 .
7. Janssen LJ. Isoprostanes: an overview and putative roles in pulmonary pathophysiology. Am. J. Physiol. Lung Cell Mol. Physiol.. 280. 6. L1067–82. 2001. 11350785. 10.1152/ajplung.2001.280.6.L1067. 2007-11-02. free.