Free radical biology & medicine
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Free Radic. Biol. Med. · Feb 2008
Oxidative lipidomics of gamma-irradiation-induced intestinal injury.
Although gamma-irradiation-induced tissue injury has been associated with lipid peroxidation, the individual phospholipid molecular targets have not been identified. We employed oxidative lipidomics to qualitatively and quantitatively characterize phospholipid peroxidation in a radiosensitive tissue, the small intestine, of mice exposed to total body irradiation (TBI) (10 and 15 Gy). Using electrospray ionization mass spectrometry we found that the major classes of intestine phospholipids-phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol-included clusters with highly oxidizable molecular species containing docosahexaenoic fatty acid. ⋯ More abundant phospholipids-phosphatidylcholine and phosphatidylethanolamine-did not reveal any oxidative stress responses despite the presence of highly oxidizable docosahexaenoic fatty acid residues in their molecular species. A marked activation of caspases 3/7 that was detected in the intestine of gamma-irradiated mice indicates the involvement of apoptotic cell death in the TBI injury. Given that oxidized molecular species of cardiolipin and phosphatidylserine accumulate during apoptosis of different cells in vitro we speculate that cardiolipin and phosphatidylserine oxidation products may be useful as potential biomarkers of gamma-irradiation-induced intestinal apoptosis in vivo and may represent a promising target for the discovery of new radioprotectors and radiosensitizers.