(±)9(10)-DiHOME-d4 (Synonyms: Leukotoxin diold4)

(±)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)