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PII‐14
Author(s) -
Brooks J. D.,
Yin H.,
Milne G. L.,
Morrow J. D.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.139
Subject(s) - isoprostanes , in vivo , dioxolane , chemistry , pharmacology , class (philosophy) , medicinal chemistry , biochemistry , medicine , computer science , biology , oxidative stress , genetics , lipid peroxidation , artificial intelligence
BACKGROUND/AIMS Free radical‐catalyzed lipid autoxidation of polyunsaturated fatty acids such as arachidonic acid occurs in intact phospholipids, and the accumulation of oxidized phospholipids in vivo has been implicated in a number of diseases such as atherosclerosis. The oxidation of arachidonic acid creates a complex set of biologically active compounds including hydroperoxides, endoperoxides, monocyclic peroxides, and serial cyclic peroxides. We hypothesized that a novel class of molecules with both a bicyclic endoperoxide and a dioxolane peroxide moiety–termed dioxolane‐isoprostanes –would form in vivo from arachidonyl‐containing phospholipids. METHODS Structural characterization of these novel products was performed using Ag + and Na + ionspray mass spectrometry methods. RESULTS Utilizing mass spectrometry, we have confirmed the structures of dioxolane‐isoprostane phospholipids. As expected, based on the free‐radical mechanism of arachidonic acid oxidation, we have found that only 12‐ and 8‐series peroxyl radicals can cyclize to form dioxolane‐isoprostanes. These results suggest a rationale for our previously reported finding that 5‐ and 15‐series isoprostanes are the major regioisomers in vivo . CONCLUSIONS Novel arachidonic acid autoxidation products–dioxolane‐isoprostanes–were definitively identified in vivo . Clinical Pharmacology & Therapeutics (2005) 79 , P39–P39; doi: 10.1016/j.clpt.2005.12.139