Abstract:
:Although the existence of halogenated lipids in lower organisms has been known for many years, it is only since the 1990s that interest in their occurrence in mammalian systems has developed. Chlorinated (and other halogenated) lipids can arise from oxidation by hypohalous acids, such as HOCl, which are products of the phagocytic enzyme myeloperoxidase and are generated during inflammation. The major species of chlorinated lipids investigated to date are chlorinated sterols, fatty acid and phospholipid chlorohydrins, and alpha-chloro fatty aldehydes. While all of these chlorinated lipids have been shown to be produced in model systems from lipoproteins to cells subjected to oxidative stress, as yet only alpha-chloro fatty aldehydes, such as 2-chlorohexadecanal, have been detected in clinical samples or animal models of disease. alpha-Chloro fatty aldehydes and chlorohydrins have been found to have a number of potentially pro-inflammatory effects ranging from toxicity to inhibition of nitric oxide synthesis and upregulation of vascular adhesion molecules. Thus evidence is building for a role of chlorinated lipids in inflammatory disease, although much more research is required to establish the contributions of specific compounds in different disease pathologies. Preventing chlorinated lipid formation and indeed other HOCl-induced damage, via the inhibition of myeloperoxidase, is an area of growing interest and may lead in the future to antimyeloperoxidase-based antiinflammatory therapy. However, other chlorinated lipids, such as punaglandins, have beneficial effects that could offer novel therapies for cancer.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Spickett CMdoi
10.1016/j.pharmthera.2007.06.002subject
Has Abstractpub_date
2007-09-01 00:00:00pages
400-9issue
3eissn
0163-7258issn
1879-016Xpii
S0163-7258(07)00111-8journal_volume
115pub_type
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