(±)12(13)-DiHOME-d4 (Synonyms: Isoleukotoxin diold4)

(±)12(13)-DiHOME-d₄ is intended for use as an internal standard for the quantification of (±)12(13)-DiHOME by GC- or LC-MS. (±)12(13)-DiHOME is the diol form of (±)12(13)-EpOME, a cytochrome P450-derived epoxide of linoleic acid also known as isoleukotoxin.¹ It is formed from 12(13)-EpOME by soluble epoxide hydrolase (sEH) in neutrophils.² 12(13)-DiHOME is toxic to Sf21 cells expressing sEH and to lacZ-expressing control cells, unlike isoleukotoxin, which is only toxic to cells containing sEH.^1,2 Levels of 12(13)-DiHOME are increased in rat spinal cord following burn injury, and it enhances cold tolerance, increases fatty acid uptake into brown adipocytes, and decreases serum triglyceride levels in mice.^3,4 Levels are also elevated in bronchoalveolar lavage fluid (BALF) in humans following exposure to biodiesel exhaust and in exhaled breath condensate in patients with asthma following allergen exposure.^5,6 Plasma levels of 12(13)-DiHOME are increased immediately following moderate-intensity exercise in mice and humans, an effect that can be prevented by brown adipose tissue removal in the mouse.⁷

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.Green, D.P., Ruparel, S., Gao, X., et al.Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injuryMol. Pain12(2016) 4.Lynes, M.D., Leiria, L.O., Lundh, M., et al.The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissueNat. Med.23(5)631-637(2017) 5.Gouveia-Figueira, S., Karimpour, M., Bosson, J.A., et al.Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposureAnal. Bioanal. Chem.409(11)2967-2980(2017) 6.Nording, M.L., Yang, J., Hegedus, C.M., et al.Endogenous levels of five fatty acid metabolites in exhaled breath condensate to monitor asthma by high-performance liquid chromatography: Electrospray tandem mass spectrometryIEEE Sens. J.10(1)123-130(2010) 7.Stanford, K.I., Lynes, M.D., Takahashi, H., et al.12,13-diHOME: An exercise-induced lipokine that increases skeletal muscle fatty acid uptakeCell Metab.27(5)1111-1120(2018)