LOX-Derived Mono Hydroxy Fatty Acids

The same anti-inflammatory profile is shared by the 15-LOX-derived LA and DGLA metabolites, 13-HODE and 15-HETrE (Xi et al. 2000 Ziboh et al. 2000 Nicolaou et al. 2012). 13-HODE is one of the most abundant hydroxy fatty acids in the skin and has been shown to reverse epidermal hyperproliferation (Cho and Ziboh 1994). Recent reports have shown a possible involvement of HODE and oxo-ODE in pain, although this has not yet been explored in skin (Ruparel et al. 2012 Sisignano et al. 2013). 13-HODE can also inhibit colonic cell proliferation and has been shown 

Finally, it should be noted also that the endocannabinoids AEA and 2-AG can be hydroxylated by 12- and 15-LOX, forming the equivalent 12-hydroxy fatty acid eth-anolamides 12-HETE-EA, 15-HETE-EA, and 12-HETE-G (Rouzer and Mamett 2011 Fonseca et al. 2013) These metabolites, like their AA analogues, have shown bioactivity though more work is needed to establish their significance (Fonseca et al. 2013). 

A number of PUFA products are generated through sequential LOX reactions and transcellular metabolism involving multiple enzymes that may be native to different cell types (Sala et al. 2010). These reactions generate poly-hydroxy fatty acids such as lipoxins, resolvins, protectins, and maresins, products of AA, EPA, and DHA 

Resolvins (Rv) are derivatives of EPA and/or DHA and are now well-established as exhibiting anti-inflammatory or pro-resolving properties. They were first identi-hed in a murine air pouch model by Serhan in 2000 (Serhan et al. 2000), and since then have been both applied and detected in various animal inflammatory disease models (i.e., colitis, ischemia-reperfusion injury, wound healing) and human nutritional intervention/disease studies (Kasuga et al. 2008 Bento et al. 2011 Norling et al. 2011 Giera et al. 2012 Mas et al. 2012). 

Protectins (PDl) or Neuroprotectin Dl (NPDl) have been identified in the brain and other CNS model systans, and were first reported in 2003 (Hong et al. 2003). In other disease models not related to the brain, PDl has been found to have both antiinflammatory and protective properties in a wide range of pathophysiological models including ischemic stroke, obesity-insulin resistance and peritonitis amongst others 

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