Quantification of 24 circulating endocannabinoids, endocannabinoid-related compounds, and their phospholipid precursors in human plasma by UHPLC-MS/MS

Röhrig, Waldemar; Achenbach, Susanne; Deutsch, Birgit; Pischetsrieder, Monika

doi:10.1194/jlr.d094680

Cited by 24 publications

(12 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we refrained from selecting control samples from a separate cohort, as conducted in some COVID-19 studies, commonly incorporating healthy controls. Combining cohorts can lead to technical bias due to varying blood collection protocols and processing conditions, specifically affecting the less-stable endocannabinoids and oxylipins [ 76 ]. The aspects of collection, storage, and processing of blood samples are thoroughly discussed elsewhere [ 77 , 78 , 79 , 80 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers

et al. 2022

View full text Add to dashboard Cite

COVID-19 is characterised by a dysregulated immune response, that involves signalling lipids acting as mediators of the inflammatory process along the innate and adaptive phases. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyse over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). The second publication in a series reports the results of quantitative LC-MS/MS profiling of 63 small lipids including oxylipins, free fatty acids, and endocannabinoids. Compared to samples taken from ward patients, intensive care unit (ICU) patients had 2–4-fold lower levels of arachidonic acid (AA) and its cyclooxygenase-derived prostanoids, as well as lipoxygenase derivatives, exhibiting negative correlations with inflammation markers. The same derivatives showed 2–5-fold increases in recovering ward patients, in paired comparison to early hospitalisation. In contrast, ICU patients showed elevated levels of oxylipins derived from poly-unsaturated fatty acids (PUFA) by non-enzymatic peroxidation or activity of soluble epoxide hydrolase (sEH), and these oxylipins positively correlated with markers of macrophage activation. The deficiency in AA enzymatic products and the lack of elevated intermediates of pro-resolving mediating lipids may result from the preference of alternative metabolic conversions rather than diminished stores of PUFA precursors. Supporting this, ICU patients showed 2-to-11-fold higher levels of linoleic acid (LA) and the corresponding fatty acyl glycerols of AA and LA, all strongly correlated with multiple markers of excessive immune response. Our results suggest that the altered oxylipin metabolism disrupts the expected shift from innate immune response to resolution of inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The implications of the endocannabinoid system and its role in human health have become an area of increasing Table 2 Nutritional composition of habitual diets of all the study participants and by sexes interest over the last decade [5]. To date, only a limited number of studies have actually measured ECs, NAEs and NAPEs in human biological fluids with circulating ECs reported in the range 0.2-9.4 ng/mL (12 studies), NAEs ranging 0.5-64.6 ng/mL (10 studies), and NAPEs ranging 120.7-800.0 ng/mL (2 studies) [29,33,34,[48][49][50]. While ECs are acknowledged key mediators in the interplay between gut, microbiota and metabolic health, to the best of our knowledge, their levels and those of NAEs and NAPEs in the gastro-intestinal tract are largely unknown with only one recent human study reporting fecal concentration for single NAPE [51].…”

Section: Discussionmentioning

confidence: 99%

Endocannabinoids, endocannabinoid-like molecules and their precursors in human small intestinal lumen and plasma: does diet affect them?

et al. 2020

View full text Add to dashboard Cite

Purpose To determine the small intestinal concentration of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their precursors N-acylphosphatidylethanolamines (NAPEs) in humans. To identify relationships between those concentrations and habitual diet composition as well as individual inflammatory status. Methods An observational study was performed involving 35 participants with an ileostomy (18W/17M, aged 18–70 years, BMI 17–40 kg/m2). Overnight fasting samples of ileal fluid and plasma were collected and ECs, NAEs and NAPEs concentrations were determined by LC-HRMS. Dietary data were estimated from self-reported 4-day food diaries. Results Regarding ECs, N-arachidonoylethanolamide (AEA) was not detected in ileal fluids while 2-arachidonoylglycerol (2-AG) was identified in samples from two participants with a maximum concentration of 129.3 µg/mL. In contrast, mean plasma concentration of AEA was 2.1 ± 0.06 ng/mL and 2-AG was 4.9 ± 1.05 ng/mL. NAEs concentrations were in the range 0.72–17.6 µg/mL in ileal fluids and 0.014–0.039 µg/mL in plasma. NAPEs concentrations were in the range 0.3–71.5 µg/mL in ileal fluids and 0.19–1.24 µg/mL in plasma being more abundant in participants with obesity than normal weight and overweight. Significant correlations between the concentrations of AEA, OEA and LEA in biological fluids with habitual energy or fat intakes were identified. Plasma PEA positively correlated with serum C-reactive protein. Conclusion We quantified ECs, NAEs and NAPEs in the intestinal lumen. Fat and energy intake may influence plasma and intestinal concentrations of these compounds. The luminal concentrations reported would allow modulation of the homeostatic control of food intake via activation of GPR119 receptors located on the gastro-intestinal mucosa. Clinical trial registry number and website NCT04143139; www.clinicaltrials.gov.

show abstract

“…Over the years, many analytical methods for the quantification of the main physiologically occurring cannabinoids, namely AEA and 2-AG, in different biological samples, such as plasma, serum, tissues, saliva, cerebrospinal fluid, and hair from humans, rats, and mice, have been reported in the literature, providing important insights into the physiology and pathology of the ECS and offering new therapeutic perspectives. These analytical methods are essentially based on high-performance liquid chromatography with UV (HPLC-UV) or fluorescence (HPLC-FL) detection, HPLC or ultra-high performance liquid chromatography (UHPLC) coupled with mass spectrometry, or GC coupled with mass spectrometry (GC-MS) [32][33][34][35][36][37]. Among these methods, tandem mass spectrometry, coupled to HPLC or UHPLC-MS with stable isotope dilution, is mostly used as the lack of chromophoric or fluorescent functional groups, as well as the very low concentrations in most biological samples, makes necessary the chemical derivatization of the molecules of interest prior to the analysis, either in the HPLC-UV or the HPLC-FL analytical method.…”

Section: Detection Of Ecs In Biological Fluids Hair and Tissuesmentioning

confidence: 99%

“…Although not strictly necessary, a proper derivatization could also offer increased volatility and sensitivity in GC-MS. Nevertheless, the quantification of ECs is typically carried out by tandem mass spectrometry coupled to HPLC or UHPLC-MS with stable isotope dilution, which, as it does not need complicated sample preparations, offers high sensitivity and selectivity [35,37]. However, pretreatment of the sample may still be necessary in order to efficiently remove interfering compounds causing ion suppression or enhancement, which in electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) cannot be avoided, possibly leading to chemical and physical sample degradations.…”

Section: Detection Of Ecs In Biological Fluids Hair and Tissuesmentioning

confidence: 99%

“…Commercial devices from different producers, or custom-assembled devices, can be used for this purpose. The latter include devices outfitted with an on-line cleanup/enrichment section such as that used by Fanelli et al [34], which was strictly derived from the high throughput SPE-HPLC-MS/MS equipment utilized by Koal et al for the quantification of immunosuppressants in whole blood samples [35] and by Saba et al for the quantification of cortisol and of some of its metabolites in urine [36]. The cleanup/enrichment stage made use of an Applied Biosystems (Waltham, MA, USA) POROS perfusion column as an SPE cartridge, which worked on the basic principle of the well-known high-turbulence liquid chromatography online extraction developed by Cohesive Technologies [37].…”

Section: Detection Of Ecs In Biological Fluids Hair and Tissuesmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Cannabinoids in Bone Metabolism: A New Perspective for Bone Disorders

Saponaro

Ferrisi

Gado

et al. 2021

IJMS

View full text Add to dashboard Cite

Novel interest has arisen in recent years regarding bone, which is a very complex and dynamic tissue deputed to several functions ranging from mechanical and protective support to hematopoiesis and calcium homeostasis maintenance. In order to address these tasks, a very refined, continuous remodeling process needs to occur involving the coordinated action of different types of bone cells: osteoblasts (OBs), which have the capacity to produce newly formed bone, and osteoclasts (OCs), which can remove old bone. Bone remodeling is a highly regulated process that requires many hormones and messenger molecules, both at the systemic and the local level. The whole picture is still not fully understood, and the role of novel actors, such as the components of the endocannabinoids system (ECS), including endogenous cannabinoid ligands (ECs), cannabinoid receptors (CBRs), and the enzymes responsible for endogenous ligand synthesis and breakdown, is extremely intriguing. This article reviews the connection between the ECS and skeletal health, supporting the potential use of cannabinoid receptor ligands for the treatment of bone diseases associated with accelerated osteoclastic bone resorption, including osteoporosis and bone metastasis.

show abstract

Quantification of 24 circulating endocannabinoids, endocannabinoid-related compounds, and their phospholipid precursors in human plasma by UHPLC-MS/MS

Cited by 24 publications

References 46 publications

Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers

Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers

Endocannabinoids, endocannabinoid-like molecules and their precursors in human small intestinal lumen and plasma: does diet affect them?

The Role of Cannabinoids in Bone Metabolism: A New Perspective for Bone Disorders

Contact Info

Product

Resources

About