(±)17 hdha

(±)17-HDHA is an autoxidation product of docosahexaenoic acid in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. 17(S)-HDHA could be produced by enzymatic oxidation of DHA using soybean lipoxygenase (LO) and is the putative product of mammalian 15-LOs. 17(S)-HDHA was shown to be an inhibitor of U-46619 -induced rabbit and rat aortic smooth muscle contraction with IC50 values of 4.9 and 7.2 μM, respectively. (±)17-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

17(S)-HDHA is a primary mono-oxygenation product of docosahexaenoic acid in human whole blood, human leukocytes, and mouse brain. 17(S)-HDHA serves as a precursor to 17(S)-resolvins and has intrinsic biological activity, such as the inhibition of TNF-α-induced interleukin-1β expression in human glioma cells and inhibition of TNF-α-induced leukocyte trafficking to the mouse air pouch.

Resolvins are a group of polyhydroxylated metabolites of docosahexaenoic acid (DHA) found in the inflammatory exudates of aspirin-treated experimental animals. 17(R)-HDHA is the primary oxygenation product of DHA when exposed to aspirin-inhibited cyclooxygenase-2. 17(R)-HDHA serves as a precursor to resolvins and has intrinsic biological activity, such as the inhibition of TNFα-induced IL-1β expression in human glioma cells.

Resolvin conjugate in tissue regeneration 1 (RCTR1) is a specialized pro-resolving mediator (SPM) biosynthesized from docosahexaenoic acid by isolated human macrophages and apoptotic polymorphonuclear (PMN) neutrophils.1It has been found in human spleen and bone marrow.2RCTR1 is produced via lipoxygenase-mediated oxidation of DHA to 7(S)-8-epoxy-17(S)-HDHA, which is conjugated to glutathione.1,2,3RCTR1 (10 nM) increases phagocytosis ofE. colior apoptotic neutrophils in isolated human monocyte-derived macrophages.2It decreases chemotaxis induced by leukotriene B4in isolated human neutrophils when used at a concentration of 10 nM. RCTR1 (1 and 10 nM) accelerates tissue regeneration in planaria. Intraperitoneal administration of RCTR1 (100 ng/animal) shortens the inflammatory resolution period and decreases inflammatory exudate neutrophil infiltration in a mouse model ofE. coli-induced peritonitis. 1.Dalli, J., Ramon, S., Norris, P.C., et al.Novel proresolving and tissue-regenerative resolvin and protectin sulfido-conjugated pathwaysFASEB J.29(5)2120-2136(2015) 2.de la Rosa, X., Norris, P.C., Chiang, N., et al.Identification and complete stereochemical assignments of the new resolvin conjugates in tissue regeneration in human tissues that stimulate proresolving phagocyte functions and tissue regenerationAm. J. Pathol.188(4)950-966(2018) 3.Rodriguez, A.R., and Spur, B.W.First total synthesis of pro-resolving and tissue-regenerative resolvin sulfido-conjugatesTetrahedron Lett.58(16)1662-1668(2017)

17(R)-Resolvin D3 (17(R)-RvD3) is an aspirin-triggered epimer of resolvin D3, produced from docosahexaenoic acid (DHA) through the action of COX-2 in the presence of aspirin, via a 17(R)-hydroperoxy DHA (17(R)-HDHA) intermediary. Identified in mouse inflammatory exudates, 17(R)-RvD3 notably inhibits the transmigration of isolated human polymorphonuclear cells (PMNs) and fosters the efferocytosis of apoptotic PMNs by macrophages. Furthermore, in a mouse model of zymosan-induced peritonitis, 17(R)-RvD3 administration (10 ng animal) significantly curtails neutrophil infiltration into the peritoneal cavity and modulates cytokine levels by reducing IL-6 and increasing IL-10 in the inflammatory exudate. It engages GPR32, evidenced by activation in a β-arrestin reporter assay and augments phagocytosis more effectively in CHO cells overexpressing GPR32 compared to controls. Additionally, 17(R)-RvD3 enhances the clearance of etoposide-induced tumor cell debris by monocyte-derived macrophages in H460 human lung carcinoma.