Comparative lipidomic analysis of inflammatory mediators in the aqueous humor and tear fluid of humans and rabbits

Chistyakov, Dmitry V.; Azbukina, Nadezhda V.; Astakhova, A. A.; Goriainov, Sergei V.; Chistyakov, V. V.; Tiulina, Veronika V.; Baksheeva, Viktoriia E.; Котелин, В. И.; Федосеева, Е. В.; Zamyatnin, Andrey A.; Philippov, Pavel P.; Киселева, О. А.; Bessmertny, A. M.; Senin, Ivan I.; Iomdina, Elena N.; Sergeeva, Marina G.; Zernii, Evgeni Yu

doi:10.1007/s11306-020-1650-y

Cited by 9 publications

(12 citation statements)

References 62 publications

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“…Then, the sample was loaded, and the cartridge was washed with 2 mL of 15% methanol containing 0.1% formic acid, after which the lipids were sequentially eluted with 500 µL of anhydrous methanol and 500 µL of acetonitrile. The resulting samples were concentrated by evaporation of the solvent under a gentle stream of nitrogen and stored at −80 • C. For the identification of lipid mediators, the respective lipid extracts were analyzed using an 8040 series UPLC-MS/MS mass spectrometer (Shimadzu, Japan) in multiple-reaction monitoring mode at a unit mass resolution for both the precursor and product ions [46]. The selected molecular ions were fragmentized in the gas phase by collision-induced dissociation and analyzed by tandem (MS/MS) mass spectrometry.…”

Section: Uplc-ms/ms Conditions and Sample Preparationmentioning

confidence: 99%

Oxylipin Profiles in Plasma of Patients with Wilson’s Disease

et al. 2020

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Wilson’s disease (WD) is a rare autosomal recessive metabolic disorder resulting from mutations in the copper-transporting, P-type ATPase gene ATP7B gene, but influences of epigenetics, environment, age, and sex-related factors on the WD phenotype complicate diagnosis and clinical manifestations. Oxylipins, derivatives of omega-3, and omega-6 polyunsaturated fatty acids (PUFAs) are signaling mediators that are deeply involved in innate immunity responses; the regulation of inflammatory responses, including acute and chronic inflammation; and other disturbances related to any system diseases. Therefore, oxylipin profile tests are attractive for the diagnosis of WD. With UPLC-MS/MS lipidomics analysis, we detected 43 oxylipins in the plasma profiles of 39 patients with various clinical manifestations of WD compared with 16 healthy controls (HCs). Analyzing the similarity matrix of oxylipin profiles allowed us to cluster patients into three groups. Analysis of the data by VolcanoPlot and partial least square discriminant analysis (PLS-DA) showed that eight oxylipins and lipids stand for the variance between WD and HCs: eicosapentaenoic acid EPA, oleoylethanolamide OEA, octadecadienoic acids 9-HODE, 9-KODE, 12-hydroxyheptadecatrenoic acid 12-HHT, prostaglandins PGD2, PGE2, and 14,15-dihydroxyeicosatrienoic acids 14,15-DHET. The compounds indicate the involvement of oxidative stress damage, inflammatory processes, and peroxisome proliferator-activated receptor (PPAR) signaling pathways in this disease. The data reveal novel possible therapeutic targets and intervention strategies for treating WD.

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Section: Uplc-ms/ms Conditions and Sample Preparationmentioning

confidence: 99%

Oxylipin Profiles in Plasma of Patients with Wilson’s Disease

et al. 2020

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“…The extraction of lipids for UPLC-MS/MS analysis was performed exactly as described in our resent study [29]. Briefly, TF samples were mixed with 2 ng of deuterated internal standard solutions and centrifuged (12,000× g, 3 min).…”

Section: Lipid Extractionmentioning

confidence: 99%

“…TF lipids were analyzed in the obtained extracts using 8040 series UPLC-MS/MS mass spectrometer (Shimadzu, Japan) in multiple-reaction monitoring mode at a unit mass resolution for both the precursor and product ions [29,35]. The lipids separation was performed by reverse-phase UPLC on Phenomenex C8 column (0.4 mL/min, sample temperature of 5 • C).…”

Section: Uplc-ms/ms Analysismentioning

confidence: 99%

“…To understand the mechanisms underlying the inflammatory reactions observed on the ocular surface, we next examined biochemical markers of the associated inflammatory pathways, focusing on lipid mediators ( Figure 2). The analysis was performed on TF, which is known to be responsible for nourishing the cornea and maintaining the immune responses of the ocular surface [29]. TF was collected using Schirmer's strips in experimental group 8 (Table 1), following the aforementioned timeline and analyzed by a high-performance, quantitative mass-spectrometric approach, developed We concluded that the pathological process in our DES model involved ocular surface inflammation, reaching a maximum on day one after anesthesia, which was accompanied by a decline in tear production and prolonged corneal damage.…”

Section: Dynamics Of Inflammation In Des: Biochemistry and Lipidomicsmentioning

confidence: 99%

“…In this model, DES is induced by exposure of the animals to general anesthesia, which diminishes the production of basal and reflex tears and decreases the stability of the tear film thereby inducing common signs of the disease [4,28]. In a more recent study, we adopted a quantitative UPLC-MS/MS-based approach to identify and characterize baseline patterns of lipid mediators in the TF of healthy rabbits and demonstrated that they did not differ significantly from that of human TF [29]. Here, we employed these approaches to characterize TF lipidomic changes in DES, focusing on PUFAs, oxylipins and phospholipid derivatives contributing to the regulation of inflammation, and to find correlations between these changes and the pathophysiological and biochemical signs of the disease.…”

Section: Introductionmentioning

confidence: 99%

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Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

et al. 2020

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Dry eye syndrome (DES) is characterized by decreased tear production and stability, leading to desiccating stress, inflammation and corneal damage. DES treatment may involve targeting the contributing inflammatory pathways mediated by polyunsaturated fatty acids and their derivatives, oxylipins. Here, using an animal model of general anesthesia-induced DES, we addressed these pathways by characterizing inflammatory changes in tear lipidome, in correlation with pathophysiological and biochemical signs of the disease. The decline in tear production was associated with the infiltration of inflammatory cells in the corneal stroma, which manifested one to three days after anesthesia, accompanied by changes in tear antioxidants and cytokines, resulting in persistent damage to the corneal epithelium. The inflammatory response manifested in the tear fluid as a short-term increase in linoleic and alpha-linolenic acid-derived oxylipins, followed by elevation in arachidonic acid and its derivatives, leukotriene B4 (5-lipoxigenase product), 12-hydroxyeicosatetraenoic acid (12-lipoxigeanse product) and prostaglandins, D2, E2 and F2α (cyclooxygenase products) that was observed for up to 7 days. Given these data, DES was treated by a novel ophthalmic formulation containing a dimethyl sulfoxide-based solution of zileuton, an inhibitor of 5-lipoxigenase and arachidonic acid release. The therapy markedly improved the corneal state in DES by attenuating cytokine- and oxylipin-mediated inflammatory responses, without affecting tear production rates. Interestingly, the high efficacy of the proposed therapy resulted from the synergetic action of its components, namely, the general healing activity of dimethyl sulfoxide, suppressing prostaglandins and the more specific effect of zileuton, downregulating leukotriene B4 (inhibition of T-cell recruitment), as well as upregulating docosahexaenoic acid (activation of resolution pathways).

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