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Elisabetta Murru - One of the best experts on this subject based on the ideXlab platform.
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effect of acute administration of pistacia lentiscus l essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion
Lipids in Health and Disease, 2012Co-Authors: Marina Quartu, Maria Pina Serra, Marianna Boi, Giuliano Pillolla, Tiziana Melis, Laura Poddighe, Marina Del Fiacco, Danilo Falconieri, Gianfranca Carta, Elisabetta MurruAbstract:Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (Pea) and oleoylethanolamide (OEA). Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where Pea and OEA levels and DHA biosynthesis increase. It is suggested that the increase of Pea and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.
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Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion
Lipids in Health and Disease, 2012Co-Authors: Marina Quartu, Maria Pina Serra, Giuliano Pillolla, Tiziana Melis, Laura Poddighe, Danilo Falconieri, Gianfranca Carta, Elisabetta Murru, Marina Del Fiacco, Lina CordedduAbstract:Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (Pea) and oleoylethanolamide (OEA). Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where Pea and OEA levels and DHA biosynthesis increase. It is suggested that the increase of Pea and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.
Marina Quartu - One of the best experts on this subject based on the ideXlab platform.
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effect of acute administration of pistacia lentiscus l essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion
Lipids in Health and Disease, 2012Co-Authors: Marina Quartu, Maria Pina Serra, Marianna Boi, Giuliano Pillolla, Tiziana Melis, Laura Poddighe, Marina Del Fiacco, Danilo Falconieri, Gianfranca Carta, Elisabetta MurruAbstract:Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (Pea) and oleoylethanolamide (OEA). Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where Pea and OEA levels and DHA biosynthesis increase. It is suggested that the increase of Pea and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.
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Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion
Lipids in Health and Disease, 2012Co-Authors: Marina Quartu, Maria Pina Serra, Giuliano Pillolla, Tiziana Melis, Laura Poddighe, Danilo Falconieri, Gianfranca Carta, Elisabetta Murru, Marina Del Fiacco, Lina CordedduAbstract:Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (Pea) and oleoylethanolamide (OEA). Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where Pea and OEA levels and DHA biosynthesis increase. It is suggested that the increase of Pea and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.
David A Barrett - One of the best experts on this subject based on the ideXlab platform.
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An Analysis of Endocannabinoid Concentrations and Mood Following Singing and Exercise in Healthy Volunteers
Frontiers Media S.A., 2018Co-Authors: Nicole L. Stone, David A Barrett, Catharine A Ortori, Sophie A. Millar, Philip J. J. Herrod, Valerie A. Mellon, Saoirse E. O’sullivanAbstract:The euphoric feeling described after running is, at least in part, due to increased circulating endocannabinoids (eCBs). eCBs are lipid signaling molecules involved in reward, appetite, mood, memory and neuroprotection. The aim of this study was to investigate whether activities other than running can increase circulating eCBs. Nine healthy female volunteers (mean 61 years) were recruited from a local choir. Circulating eCBs, haemodynamics, mood and hunger ratings were measured before and immediately after 30 min of dance, reading, singing or cycling in a fasted state. Singing increased plasma levels of anandamide (AEA) by 42% (P < 0.05), palmitoylethanolamine (Pea) by 53% (P < 0.01) and oleoylethanolamine (OEA) by 34% (P < 0.05) and improved positive mood and emotions (P < 0.01), without affecting hunger scores. Dancing did not affect eCB levels or hunger ratings, but decreased negative mood and emotions (P < 0.01). Cycling increased OEA levels by 26% (P < 0.05) and tended to decrease how hungry volunteers felt, without affecting mood. Reading increased OEA levels by 28% (P < 0.01) and increased the desire to eat. Plasma AEA levels were positively correlated with how full participants felt (P < 0.05). Plasma OEA levels were positively correlated with positive mood and emotions (P < 0.01). All three ethanolamines were positively correlated with heart rate (HR; P < 0.0001). These data suggest that activities other than running can increase plasma eCBs associated with changes in mood or appetite. Increases in eCBs may underlie the rewarding and pleasurable effects of singing and exercise and ultimately some of the long-term beneficial effects on mental health, cognition and memory
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lack of effect of chronic pre treatment with the faah inhibitor urb597 on inflammatory pain behaviour evidence for plastic changes in the endocannabinoid system
British Journal of Pharmacology, 2012Co-Authors: Bright N Okine, David A Kendall, David A Barrett, Annie Patel, Andrew J. Bennett, Stephen P.h. Alexander, Leonie M Norris, Stephen G. Woodhams, James J. Burston, Victoria ChapmanAbstract:BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day rePeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (Pea) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not rePeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, Pea and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, Pea and OEA in the spinal cord, compared with those after rePeated administration. Single and rePeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following rePeated administration of low dose URB597 in this model of inflammatory pain.
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Lack of effect of chronic pre‐treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system
British Journal of Pharmacology, 2012Co-Authors: Bright N Okine, David A Kendall, David A Barrett, Annie Patel, Andrew J. Bennett, Stephen P.h. Alexander, Leonie M Norris, Stephen G. Woodhams, James J. Burston, Victoria ChapmanAbstract:BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day rePeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (Pea) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not rePeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, Pea and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, Pea and OEA in the spinal cord, compared with those after rePeated administration. Single and rePeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following rePeated administration of low dose URB597 in this model of inflammatory pain.
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entourage effects of n palmitoylethanolamide and n oleoylethanolamide on vasorelaxation to anandamide occur through trpv1 receptors
British Journal of Pharmacology, 2008Co-Authors: David A Barrett, Michael D RandallAbstract:Background and purpose: The endocannabinoid N-arachidonoylethanolamide (anandamide) is co-synthesized with other N-acylethanolamides, namely N-palmitoylethanolamide (Pea) and N-oleoylethanolamide (OEA), which have been shown to potentiate anandamide responses (so-called ‘entourage effects’) in non-vascular tissues. It remains unclear whether such interactions occur in the circulation. Experimental approach: In rat isolated small mesenteric arteries, the effects of Pea and OEA on relaxation to anandamide and tissue contents of the N-acylethanolamides were examined under myographic conditions. Key results: Anandamide-induced relaxation was potentiated by pretreatment with Pea (10 μM) or OEA (1 μM), or in combination. The potentiation by Pea and OEA was endothelium-independent and abolished by treatment with capsaicin (10 μM), which desensitizes the transient receptor potential vanilloid type 1 (TRPV1) receptor system, or by the TRPV1 receptor antagonist, N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791) (2 μM). It was also observed at molar ratios of anandamide and Pea (or OEA) similar to those found in mesenteric arteries. Pea and inhibition of anandamide hydrolysis by 3′-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate (URB597) (1 μM) additively potentiated anandamide responses. On the other hand, Pea and OEA also induced vasorelaxation per se (rank order of potency: anandamide>OEA>Pea), but relaxation to the three N-acylethanolamides displayed different sensitivity to treatment with capsaicin, SB366791 and URB597. For example, relaxations to anandamide and OEA, but not Pea, were attenuated by both capsaicin and SB366791. Conclusion and implications: This study shows that Pea and OEA potentiate relaxant responses to anandamide through TRPV1 receptors in rat small mesenteric arteries. The congeners also induce vasorelaxation per se, suggesting a function for the N-acylethanolamides in vascular control. British Journal of Pharmacology (2008) 155, 837–846; doi:10.1038/bjp.2008.324; published online 11 August 2008
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quantitative profiling of endocannabinoids and related compounds in rat brain using liquid chromatography tandem electrospray ionization mass spectrometry
Analytical Biochemistry, 2007Co-Authors: Denise Richardson, David A Kendall, Victoria Chapman, Catharine A Ortori, David A BarrettAbstract:Abstract A sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method is described for the simultaneous identification and quantification of eight endocannabinoid (EC) or related “entourage” compounds in rat brain tissue. Analytes were extracted and purified from rat brain tissue using an ethyl acetate/hexane solvent extraction, followed by a solid phase extraction (SPE) protocol. Chromatographic separation was achieved using a gradient elution, with a mobile phase of acetonitrile, formic acid, and ammonium acetate, at pH 3.6. A Thermo Hypersil C8 HyPurity Advance column (100 × 2.1 mm i.d., 3 μm) was used with a flow rate of 0.3 ml/min). Anandamide (AEA), 2-arachidonyl glycerol (2-AG), 2-arachidonylglyceryl ether (noladin ether), O-arachidonyl ethanolamide (virodhamine), 2-linoleoyl glycerol (2-LG), arachidonyl glycine, oleoyl ethanolamide (OEA), and palmitoyl ethanolamide (Pea) were quantified by positive ion tandem electrospray ionization mass spectrometry. Internal standards were deuterated AEA, deuterated 2-AG, and heptadecanoyl ethanolamide (HEA). Linearity was proven over the range of 25 fmol to 250 pmol, with a limit of detection of 25 fmol on column for all analytes except 2-AG, noladin ether, and 2-LG (250 fmol). This corresponded to a limit of quantification in biological tissue of 10 pmol/g for all analytes except 2-AG (100 pmol/g). Intra- and interday precision in biological tissue was routinely approximately 20% or lower, and accuracy was between 65% and 155%. This method was used to quantitatively profile regional differences in nine discrete rat brain regions for AEA, 2-AG, 2-LG, OEA, Pea, noladin ether, virodhamine, and arachidonyl glycine.
Justin C. Konje - One of the best experts on this subject based on the ideXlab platform.
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Expression and Function of the Endocannabinoid Modulating Enzymes Fatty Acid Amide Hydrolase and N-Acylphosphatidylethanolamine-Specific Phospholipase D in Endometrial Carcinoma.
Frontiers in oncology, 2019Co-Authors: Thangesweran Ayakannu, Anthony H. Taylor, Mauro Maccarrone, Monica Bari, Nicoletta Mastrangelo, Justin C. KonjeAbstract:Background: The concentrations of three N-acylethanolamines (NAEs), anandamide (AEA), N-oleoylethanolamide (OEA) and N-palmitylethanolamide (Pea) are increased in the endometria of women with endometrial cancer (EC). It is widely accepted that plasma levels of these three NAEs are regulated by the actions of the N-acylphoshatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), enzymes that are, respectively, rate-limiting synthesis and degradative. The expression and activity of these enzymes has not previously been studied in EC. Methods: FAAH activity in peripheral blood lymphocytes, and transcript and protein expression for FAAH and NAPE-PLD in EC tissues were measured using enzyme, quantitative RT-PCR and histomorphometric analyses of immunoreactive tissue sections, respectively. Samples were provided by 6 postmenopausal women (controls) and 34 women with histologically diagnosed EC. Results: Peripheral lymphocyte FAAH activity was unaffected in women with EC when compared with women devoid of disease. The FAAH transcript expression level was 75% lower in EC whilst NAPE-PLD levels were non-significantly increased. A significant tumour type-dependent 70-90% decrease in FAAH protein and significant 4- to 14-fold increase in NAPE-PLD protein was observed in the malignant tissue that correlated with advancing disease, complementing the transcript data. Correlation analyses also confirmed that increased tissue NAE concentrations were inversely related to FAAH expression and directly correlated to NAPE-PLD expression and the NAPE-PLD/FAAH ratio. Conclusion: These data support the previously observed tissue levels of AEA, OEA and Pea and a role for NAE metabolism in the pathogenesis of EC.
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Identification of Novel Predictive Biomarkers for Endometrial Malignancies: N-Acylethanolamines.
Frontiers in oncology, 2019Co-Authors: Thangesweran Ayakannu, Anthony H. Taylor, Timothy H. Marczylo, Mauro Maccarrone, Justin C. KonjeAbstract:Objective: To identify new biochemical markers for endometrial cancer (EC). Recent evidence suggests that members of the endocannabinoid system (N-acylethanolamines) that bind to and activate receptors that are dysregulated in EC are involved in this tumour's biology. These observations suggest increased N-acylethanolamine levels in the tissue that might apPear in plasma and could be used as disease biomarkers. Methods: N-arachidonoylethanolamine (anandamide, AEA) and the N-acylethanolamine substances, N-oleoylethanolamine (OEA), and N-palmitoylethanolamine (Pea) were quantified in plasma and endometrial tissue collected from 31 EC and seven atrophic controls using UHPLC-MS/MS. Receiver-operating characteristics (ROC) and logistic regression were used to determine diagnostic accuracy. Cannabinoid receptor 1 (CB1) and 2 (CB2) protein levels were determined by specific immunohistochemistry and histomorphometric analyses. Correlations between plasma and tissue levels of the three N-acylethanolamines and tissue levels of the three N-acylethanolamines and CB1 and CB2 receptor expression levels were determined using correlation analysis. Results: Plasma and tissue AEA and Pea levels were significantly (p 1.36 nM); sensitivity of 73.3%, specificity of 100% for plasma Pea (>27.5 nM); and sensitivity of 93.3%, specificity of 28.6% for plasma OEA (>4.97 nM). Logistic regression increased the area under the ROC curve (AUC) from 0.781 for AEA, 0.857 for Pea, and 0.543 for OEA to a combined AUC of 0.933 for EC diagnosis. Significant inverse correlations between tissue AEA (R2 = 0.343, p = 0.003) and Pea (R2 = 0.384, p < 0.0001) levels and CB1 expression were observed. No correlation between tissue levels of OEA and CB1 and tissue levels of any of the three N-acylethanolamines and CB2 protein expression were observed, except in the type 1 EC patients. Conclusion: Since plasma AEA and Pea are significantly elevated in patients with EC and a reflection of production by the endometrial tumour, then these lipids have the potential to be useful biomarkers for the early diagnosis of EC.
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Prediction of preterm labour from a single blood test: The role of the endocannabinoid system in predicting preterm birth in high-risk women
2019Co-Authors: P Bachkangi, Mauro Maccarrone, Monica Bari, Ah Taylor, Justin C. KonjeAbstract:Objective: To determine if plasma concentrations of the N-acylethanolamines (NAEs) N-arachidonoylethanolamine (AEA), N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (Pea) increase in women at high risk for preterm birth (PTB) and whether these could be used to predict preterm delivery and if so, how they compare with current methods. Design: Prospective cohort study. Setting: A large UK teaching hospital. Population: 217 pregnant women were recruited between 24 and 34 gestational weeks at ‘high-risk’ for PTB, recruited from a prematurity prevention clinic or antenatal wards. Methods: Plasma AEA, OEA, and Pea concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry whilst FAAH enzyme activity was measured by fluorometric radiometric assay and CL by ultrasound scan. The clinical usefulness of these measurements were determined by ROC and multivariate analyses. Results: AEA and Pea concentrations were significantly higher in women who delivered prematurely. An AEA concentration >1.095 nM predicted PTB, the gestational age at delivery and the recruitment to delivery interval (RTDI). A Pea concentration >17.50 nM only predicted PTB; FAAH enzyme activity was not related to these changes. Multivariate analysis (all variables) generated an equation to accurately predict the RTDI. Conclusions: A single plasma AEA or Pea measurement can predict PTB. A single AEA measurement predicts the gestational age of delivery and the remaining period of pregnancy with reasonable accuracy and better than existing conventional tests thus offering a better window for primary prevention of PTB
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Expression and Function of the Endocannabinoid Modulating Enzymes Fatty Acid Amide Hydrolase and N-Acylphosphatidylethanolamine-Specific Phospholipase D in Endometrial Carcinoma
2019Co-Authors: Thangesweran Ayakannu, Anthony H. Taylor, Mauro Maccarrone, Monica Bari, Nicoletta Mastrangelo, Justin C. KonjeAbstract:Background: The concentrations of three N-acylethanolamines (NAEs), anandamide (AEA), N-oleoylethanolamide (OEA), and N-palmitylethanolamide (Pea) are increased in the endometria of women with endometrial cancer (EC). It is widely accepted that plasma levels of these three NAEs are regulated by the actions of the rate-limiting enzymes N-acylphoshatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), which are synthesizing and degradative, respectively. The expression and activity of these enzymes have not previously been studied in EC. Methods: FAAH activity in peripheral blood lymphocytes, and transcript and protein expression for FAAH and NAPE-PLD in EC tissues were measured using enzyme, quantitative RT-PCR, and histomorphometry (of immunoreactive tissue sections), respectively. Samples were from 6 post-menopausal women with atrophic endometria (controls) and 34 women with histologically diagnosed EC. Concentrations of the three NAEs also measured in plasma and tissues were correlated with lymphocytic FAAH activity and the NAPE-PLD and FAAH transcript and protein levels. Results: Peripheral lymphocyte FAAH activity was unaffected in women with EC compared to controls. The FAAH transcript expression level was significantly (p < 0.0001) 75% lower in EC whilst NAPE-PLD levels were not significantly (p = 0.798) increased. In line with the transcript data, a significant (p < 0.0001) tumor type-dependent 70–90% decrease in FAAH protein and significant 4- to 14-fold increase in NAPE-PLD protein (p < 0.0001) was observed in the malignant tissue with more advanced disease having lower FAAH and higher NAPE-PLD expression than less advanced disease. Correlation analyses also confirmed that tissue NAE concentrations were inversely related to FAAH expression and directly correlated to NAPE-PLD expression and the NAPE-PLD/FAAH ratio. Conclusion: These data support our previous observation of tissue levels of AEA, OEA, and Pea and a role for NAE metabolism in the pathogenesis of EC.
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Relationship between seminal plasma levels of anandamide congeners palmitoylethanolamide and oleoylethanolamide and semen quality.
Fertility and sterility, 2014Co-Authors: Akwasi A. Amoako, Anthony H. Taylor, Timothy H. Marczylo, Janine Elson, Jonathon M. Willets, Justin C. KonjeAbstract:Objective To determine whether changes in seminal plasma concentrations of the endogenous lipid signaling molecules palmitoylethanolamide (Pea) and oleoylethanolamide (OEA) have significant effects on sperm quality. Design Biochemical and physiological studies of human seminal plasma and spermatozoa. Setting Academic tertiary care medical center. Patient(s) Ninety men attending an infertility clinic for semen analysis. Intervention(s) Palmitoylethanolamide and OEA extracted from seminal plasma were quantified by ultra high-performance liquid chromatography (HPLC)-tandem mass spectrometry. Patient sperm from semen with normal parameters were exposed in vitro to Pea or OEA to determine effects on sperm motility, viability, and mitochondrial activity. Main Outcome Measure(s) The relationship between seminal plasma concentrations of Pea and OEA and sperm quality and the effect of these compounds on sperm motility, viability, and mitochondria activity in vitro. Result(s) Palmitoylethanolamide and OEA concentrations in seminal plasma were lower in men with asthenozoospermia and oligoasthenoteratozospermia compared with men with normal semen parameters. Palmitoylethanolamide and OEA rapidly and significantly improved sperm motility and maintained viability without affecting mitochondria activity in vitro. Conclusion(s) Maintenance of normal Pea and OEA tone in human seminal plasma may be necessary for the preservation of normal sperm function and male fertility. Exocannabinoids found in Cannabis , such as delta-9-tetrahydrocannabinol and cannabidiol, could compete with these endocannabinoids upsetting their finely balanced, normal functioning and resulting in male reproductive failure.
Lina Cordeddu - One of the best experts on this subject based on the ideXlab platform.
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Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion
Lipids in Health and Disease, 2012Co-Authors: Marina Quartu, Maria Pina Serra, Giuliano Pillolla, Tiziana Melis, Laura Poddighe, Danilo Falconieri, Gianfranca Carta, Elisabetta Murru, Marina Del Fiacco, Lina CordedduAbstract:Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (Pea) and oleoylethanolamide (OEA). Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where Pea and OEA levels and DHA biosynthesis increase. It is suggested that the increase of Pea and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.