1.02011-09-21 01:23:21 UTC2015-07-21 06:59:06 UTCFDB02736817-HDoHEDocosahexaenoic 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 acid17-Hdhe17-hydroxy-4,7,10,13,15,19-docosahexaenoate17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid17-hydroxy-DHA17-Hydroxydocosahexaenoate17-Hydroxydocosahexaenoic acidC22H32O3344.4877344.2351448917-hydroxydocosa-4,7,10,13,15,19-hexaenoic acid17-hydroxydocosa-4,7,10,13,15,19-hexaenoic acid90780-52-2CCC=CCC(O)C=CC=CCC=CCC=CCC=CCCC(O)=OInChI=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 acidsOrganic compoundsLipids and lipid-like moleculesFatty AcylsFatty acids and conjugatesAliphatic acyclic compoundsCarbonyl compoundsCarboxylic acidsHydrocarbon derivativesHydroxy fatty acidsMonocarboxylic acids and derivativesOrganic oxidesSecondary alcoholsUnsaturated fatty acidsAlcoholAliphatic acyclic compoundCarbonyl groupCarboxylic acidCarboxylic acid derivativeHydrocarbon derivativeHydroxy fatty acidMonocarboxylic acid or derivativesOrganic oxideOrganic oxygen compoundOrganooxygen compoundSecondary alcoholUnsaturated fatty acidVery long-chain fatty acidSolidlogp5.96logs-5.47solubility1.17e-03 g/llogp5.52pka_strongest_acidic4.89pka_strongest_basic-1.6iupac17-hydroxydocosa-4,7,10,13,15,19-hexaenoic acidaverage_mass344.4877mono_mass344.23514489smilesCCC=CCC(O)C=CC=CCC=CCC=CCC=CCCC(O)=OformulaC22H32O3inchiInChI=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)inchikeySWTYBBUBEPPYCX-UHFFFAOYSA-Npolar_surface_area57.53refractivity112.9polarizability40.76rotatable_bond_count14acceptor_count3donor_count2physiological_charge-1formal_charge0Specdb::MsMs3397441Specdb::MsMs3397442Specdb::MsMs3397443Specdb::MsMs3397444Specdb::MsMs3397445Specdb::MsMs3397446Specdb::CMs107458Specdb::CMs119835Specdb::CMs128653Specdb::CMs130221Specdb::CMs811870HMDB10213#<Reference:0x0000555675660640>#<Reference:0x0000555675660460>#<Reference:0x0000555675660230>AnatidaeType 1specificAnatidae8830BeefaloType 1specificBos taurus X Bison bison297284BisonType 1specificBison bison9901BuffaloType 1specificBubalus bubalis89462Cattle (Beef, Veal)Type 1specificBos taurus9913ChickenType 1specificGallus gallus9031Columbidae (Dove, Pigeon)Type 1specificColumbidae8930DeerType 1specificCervidae9850Domestic goatType 1specificCapra aegagrus hircus9925Domestic pigType 1specificSus scrofa domestica9825ElkType 1specificCervus canadensis1574408EmuType 1specificDromaius novaehollandiae8790European rabbitType 1specificOryctolagus9984Greylag gooseType 1specificAnser anser8843Guinea henType 1specificNumida meleagris8996HorseType 1specificEquus caballus9796Mallard duckType 1specificAnas platyrhynchos8839Mountain hareType 1specificLepus timidus62621Mule deerType 1specificOdocoileus9871OstrichType 1specificStruthio camelus8801PheasantType 1specificPhasianus colchicus9054QuailType 1specificPhasianidae9005RabbitType 1specificLeporidae9979Rock ptarmiganType 1specificLagopus muta64668Sheep (Mutton, Lamb)Type 1specificOvis aries9940SquabType 1specificColumba8931TurkeyType 1specificMeleagris gallopavo9103Velvet duckType 1specificMelanitta fusca371864Wild boarType 1specificSus scrofa9823