(±)9(10)-DiHOME-d4 is intended for use as an internal standard for the quantification of (±)9(10)-DiHOME by GC- or LC-MS. (±)9(10)-DiHOME is the diol form of (±)9(10)-EpOME , a cytochrome P450-derived epoxide of linoleic acid also known as leukotoxin.1 It is formed from 9(10)-EpOME by soluble epoxide hydrolase (sEH) in neutrophils.2 9(10)-DiHOME has been used as a plasma biomarker for sEH activity in vivo.3 It is toxic to Sf21 cells expressing sEH and to lacZ-expressing control cells, unlike leukotoxin, which is only toxic to cells containing sEH.1,2 A mixture of 9(10)- and 12(13)-DiHOME induces cell death in rabbit renal proximal tubule cells concomitant with mitochondrial respiration dysfunction and induces lung injury, respiratory distress, and mortality in mice.4,5 9(10)-DiHOME is a toxic lipid mediator involved in acute respiratory distress syndrome (ARDs), a common and often fatal complication in severe burn victims.2,4 Levels of 9(10)-DiHOME are increased in bronchoalveolar lavage fluid (BALF) from women, but not men, with chronic obstructive pulmonary disease (COPD).3 BALF levels are also increased in patients with allergic asthma following provocation with birch pollen compared to patients without allergic asthma.6
1.Greene, J.F., Williamson, K.C., Newman, J.W., et al.Metabolism of monoepoxides of methyl linoleate: Bioactivation and detoxificationArch. Biochem. Biophys.376(2)420-432(2000) 2.Moghaddam, M.F., Grant, D.F., Cheek, J.M., et al.Bioactivation of leukotoxins to their toxic diols by epoxide hydrolaseNat. Med.3(5)562-566(1997) 3.Zhu, P., Peck, B., Licea-Perez, H., et al.Development of a semi-automated LC/MS/MS method for the simultaneous quantitation of 14,15-epoxyeicosatrienoic acid, 14,15-dihydroxyeicosatrienoic acid, leukotoxin and leukotoxin diol in human plasma as biomarkers of soluble epoxide hydrolase activity in vivoJ. Chromatogr. B Analyt. Technol. Biomed. Life Sci.879(25)2487-2493(2011) 4.Zheng, J., Plopper, C.G., Lakritz, J., et al.Leukotoxin-diol a putative toxic mediator involved in acute respiratory distress syndromeAm. J. Respir. Cell Mol. Biol.25(4)434-438(2001) 5.Moran, J.H., Weise, R., Schnellmann, R.G., et al.Cytotoxicity of linoleic acid diols to renal proximal tubular cellsToxicol. Appl. Pharmacol.146(1)53-59(1997) 6.LundstrÖm, S.L., Yang, J., KÄllberg, H.J., et al.Allergic asthmatics show divergent lipid mediator profiles from healthy controls both at baseline and following birch pollen provocationPLoS One7(3)e33780(2012)