1.0 2011-09-21 01:23:21 UTC 2015-07-21 06:59:06 UTC FDB027368 17-HDoHE Docosahexaenoic acid (DHA) is a omega-3 essential fatty acid that reduces the incidence and severity of a number of diseases. Recently, a novel series of DHA-derived lipid mediators with potent protective actions has been identified. In this study we demonstrate that dietary amplification of these DHA-derived products protects the liver from necroinflammatory injury. In vitro, supplementation of hepatocytes with DHA significantly reduced hydrogen peroxide-induced DNA damage, evaluated by the "comet assay," and oxidative stress, determined by measurement of malondialdehyde levels. In vivo, dietary supplementation of mice with DHA ameliorated carbon tetrachloride-induced necroinflammatory damage. In addition, hepatic cyclooxygenase-2 expression and PGE2 levels were significantly reduced in mice fed DHA-enriched diets. In these animals, increased hepatic formation of DHA-derived lipid mediators (i.e., 17S-hydroxy-DHA (17S-HDHA) and protectin D1) was detected by HPLC-gas chromatography/mass spectrometry analysis. Consistent with these findings, synthetic 17-HDHA abrogated genotoxic and oxidative damage in hepatocytes and decreased TNF-alpha release and 5-lipoxygenase expression in macrophages. In a transactivation assay, 17-HDHA acted in a concentration-dependent manner as a PPARgamma agonist. Taken together, these findings identify a potential role for DHA-derived products, specifically 17S-HDHA and protectin D1, in mediating the protective effects of dietary DHA in necroinflammatory liver injury. (PMID: 17056761) This fatty acyl belongs to the main class of docosanoids. (Lipid Maps) [HMDB] (+/-)-17-HDoHE (+/-)-17-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoate (+/-)-17-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docosahexaenoic acid (4Z,7Z,10Z,13Z,15E,19Z)-17-hydroxydocosa-4,7,10,13,15,19-hexaenoate (4Z,7Z,10Z,13Z,15E,19Z)-17-hydroxydocosa-4,7,10,13,15,19-hexaenoic acid (E,Z,Z,Z,Z,Z)-17-hydroxy-, 4,7,10,13,15,19-docosahexaenoate (E,Z,Z,Z,Z,Z)-17-hydroxy-, 4,7,10,13,15,19-docosahexaenoic acid 17-Hdhe 17-hydroxy-4,7,10,13,15,19-docosahexaenoate 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid 17-hydroxy-DHA 17-Hydroxydocosahexaenoate 17-Hydroxydocosahexaenoic acid C22H32O3 344.4877 344.23514489 17-hydroxydocosa-4,7,10,13,15,19-hexaenoic acid 17-hydroxydocosa-4,7,10,13,15,19-hexaenoic acid 90780-52-2 CCC=CCC(O)C=CC=CCC=CCC=CCC=CCCC(O)=O InChI=1S/C22H32O3/c1-2-3-15-18-21(23)19-16-13-11-9-7-5-4-6-8-10-12-14-17-20-22(24)25/h3,5-8,11-16,19,21,23H,2,4,9-10,17-18,20H2,1H3,(H,24,25) SWTYBBUBEPPYCX-UHFFFAOYSA-N belongs to the class of organic compounds known as very long-chain fatty acids. These are fatty acids with an aliphatic tail that contains at least 22 carbon atoms. Very long-chain fatty acids Organic compounds Lipids and lipid-like molecules Fatty Acyls Fatty acids and conjugates Aliphatic acyclic compounds Carbonyl compounds Carboxylic acids Hydrocarbon derivatives Hydroxy fatty acids Monocarboxylic acids and derivatives Organic oxides Secondary alcohols Unsaturated fatty acids Alcohol Aliphatic acyclic compound Carbonyl group Carboxylic acid Carboxylic acid derivative Hydrocarbon derivative Hydroxy fatty acid Monocarboxylic acid or derivatives Organic oxide Organic oxygen compound Organooxygen compound Secondary alcohol Unsaturated fatty acid Very long-chain fatty acid Solid logp 5.96 ALOGPS logs -5.47 ALOGPS solubility 1.17e-03 g/l ALOGPS logp 5.52 ChemAxon pka_strongest_acidic 4.89 ChemAxon pka_strongest_basic -1.6 ChemAxon iupac 17-hydroxydocosa-4,7,10,13,15,19-hexaenoic acid ChemAxon average_mass 344.4877 ChemAxon mono_mass 344.23514489 ChemAxon smiles CCC=CCC(O)C=CC=CCC=CCC=CCC=CCCC(O)=O ChemAxon formula C22H32O3 ChemAxon inchi InChI=1S/C22H32O3/c1-2-3-15-18-21(23)19-16-13-11-9-7-5-4-6-8-10-12-14-17-20-22(24)25/h3,5-8,11-16,19,21,23H,2,4,9-10,17-18,20H2,1H3,(H,24,25) ChemAxon inchikey SWTYBBUBEPPYCX-UHFFFAOYSA-N ChemAxon polar_surface_area 57.53 ChemAxon refractivity 112.9 ChemAxon polarizability 40.76 ChemAxon rotatable_bond_count 14 ChemAxon acceptor_count 3 ChemAxon donor_count 2 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Specdb::MsMs 3397441 Specdb::MsMs 3397442 Specdb::MsMs 3397443 Specdb::MsMs 3397444 Specdb::MsMs 3397445 Specdb::MsMs 3397446 Specdb::CMs 107458 Specdb::CMs 119835 Specdb::CMs 128653 Specdb::CMs 130221 Specdb::CMs 811870 HMDB10213 #<Reference:0x00007f093c0d9d40> #<Reference:0x00007f093c0d9b88> #<Reference:0x00007f093c0d99d0> Anatidae Type 1 specific Anatidae 8830 Beefalo Type 1 specific Bos taurus X Bison bison 297284 Bison Type 1 specific Bison bison 9901 Buffalo Type 1 specific Bubalus bubalis 89462 Cattle (Beef, Veal) Type 1 specific Bos taurus 9913 Chicken Type 1 specific Gallus gallus 9031 Columbidae (Dove, Pigeon) Type 1 specific Columbidae 8930 Deer Type 1 specific Cervidae 9850 Domestic goat Type 1 specific Capra aegagrus hircus 9925 Domestic pig Type 1 specific Sus scrofa domestica 9825 Elk Type 1 specific Cervus canadensis 1574408 Emu Type 1 specific Dromaius novaehollandiae 8790 European rabbit Type 1 specific Oryctolagus 9984 Greylag goose Type 1 specific Anser anser 8843 Guinea hen Type 1 specific Numida meleagris 8996 Horse Type 1 specific Equus caballus 9796 Mallard duck Type 1 specific Anas platyrhynchos 8839 Mountain hare Type 1 specific Lepus timidus 62621 Mule deer Type 1 specific Odocoileus 9871 Ostrich Type 1 specific Struthio camelus 8801 Pheasant Type 1 specific Phasianus colchicus 9054 Quail Type 1 specific Phasianidae 9005 Rabbit Type 1 specific Leporidae 9979 Rock ptarmigan Type 1 specific Lagopus muta 64668 Sheep (Mutton, Lamb) Type 1 specific Ovis aries 9940 Squab Type 1 specific Columba 8931 Turkey Type 1 specific Meleagris gallopavo 9103 Velvet duck Type 1 specific Melanitta fusca 371864 Wild boar Type 1 specific Sus scrofa 9823