Urinary 8-EPI PGF: an index of oxidant stress in vivo*

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Summary

Isoeicosanoids are free radical catalyzed products of arachidonic acid. To explore their biology and potential utility as indices of oxidant stress, we have focused upon one isomer, 8-epi PGF. Excretion of this compound is increased in syndromes putatively associated with oxidant stress, including poisoning with paraquat and paracetemol, cigarette smoking, alcohol intake, diabetic ketosis, ARDS, and syndromes of vascular reperfusion. 8-Epi may also be formed by COX-1 in platelets and by COX-2 in monocytes, although these pathways are minor contributors to overall biosynthesis. Monocytes also retain the capacity to form 8-epi as an isoprostane when stimulated with zymosan in the presence of LDL. Identification of 8-epi in human plaque and elevated excretion in hypercholesterolemia suggest its utility in exploring the role of oxidant stress in atherosclerosis. 8-Epi may also amplify the affects of platelet agonists in the local microenvironment in syndromes where platelet activation and oxidant injury coincide.

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Supported by a SCOR grant from The National Institutes of Health (HL 54500) and research fellowships from the Health Research Board of Ireland (MPR) and the Irish Heart Foundation (MPR). Dr Garret A. FitzGerald is the Robinette Foundation Professor of Cardiovascular Medicine.