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Journal of Biosciences 2022Iron overload can induce oxidative stress, thereby inducing cell peroxidation. Arachidonic acid (ARA) is widely expressed in mammalian cells and esterified to membrane...
Iron overload can induce oxidative stress, thereby inducing cell peroxidation. Arachidonic acid (ARA) is widely expressed in mammalian cells and esterified to membrane phospholipids. To explore the effect of iron overload on the metabolism of membrane phospholipids MES23.5 cells were treated with various concentrations of ferric ammonium citrate (FAC) to induce oxidative stress. Using UHPLC (I-Class LC, Waters) coupled to a QTRAP (AB Sciex 5500) technology, the contents of 13 substances of ARA and its metabolites were detected. When the cells were given two different concentrations of FAC, we found that both high and low concentrations decrease the expression of ARA (p=0.002, p=0.02) compared with the control group. ARA has three metabolic pathways: the COX pathway, LOX pathway and CYP450 pathway. Compared with the control group, the LTB4 content in the LOX pathway was decreased (p=0.10) after treatment with lowconcentration FAC, while the LTB4 content was increased in the high-concentration treatment group (p=0.06). However, the content of 12S-HETE (p=0.23, p=0.05) in the LOX metabolic pathway decreased with increase of FAC concentration. Similarly, the content of 15S-HETE also decreased with increase of FAC concentration (p=0.17, p=0.02). The other downstream metabolites of ARA, 9S-HODE (p=0.54, p=0.18) and 13S-HODE (p=0.81, p=0.13) were not significantly changed. The contents of thromboxane B2 (TXB2), leukotriene D4 (LTD4), prostaglandin E2 (PGE2), 8-iso-prostaglandin F2α (8-iso-PGF2α), prostaglandin F2α (PGF2α), 6-keto-PGF1α, and prostaglandin D2 (PGD2) were too low to be detected in MES23.5 cells. The above results indicate that oxidative stress caused by iron overload reduces the LOX metabolic pathway of ARA.
Topics: Animals; Arachidonic Acid; Dinoprost; Leukotriene B4; Oxidative Stress; Iron Overload; Phospholipids; Hydroxyeicosatetraenoic Acids; Mammals
PubMed: 36550694
DOI: No ID Found -
Journal of Alzheimer's Disease : JAD 2016Meta-analysis has shown that smokers have significantly increased risks for Alzheimer's disease (AD), and neuroimaging studies showed that smoking alters white matter...
BACKGROUND
Meta-analysis has shown that smokers have significantly increased risks for Alzheimer's disease (AD), and neuroimaging studies showed that smoking alters white matter (WM) structural integrity.
OBJECTIVE
Herein, we characterize the effects of cigarette smoke (CS) exposures and withdrawal on WM myelin lipid composition using matrix assisted laser desorption and ionization-imaging mass spectrometry (MALDI-IMS).
METHODS
Young adult male A/J mice were exposed to air (8 weeks; A8), CS (4 or 8 weeks; CS4, CS8), or CS8 followed by 2 weeks recovery (CS8 + R). Frontal lobe WM was examined for indices of lipid and protein oxidation and lipid profile alterations by MALDI-IMS. Lipid ions were identified by MS/MS with the LIPID MAPS prediction tools database. Inter-group comparisons were made using principal component analysis and R-generated heatmap.
RESULTS
CS increased lipid and protein adducts such that higher levels were present in CS8 compared with CS4 samples. CS8 + R reversed CS8 effects and normalized the levels of oxidative stress. MALDI-IMS demonstrated striking CS-associated alterations in WM lipid profiles characterized by either reductions or increases in phospholipids (phosphatidylinositol, phosphatidylserine, phosphatidylcholine, or phosphatidylethanolamine) and sphingolipids (sulfatides), and partial reversal of CS's inhibitory effects with recovery. The heatmap hierarchical dendrogram and PCA distinguished CS exposure, duration, and withdrawal effects on WM lipid profiles.
CONCLUSION
CS-mediated WM degeneration is associated with lipid peroxidation, protein oxidative injury, and alterations in myelin lipid composition, including shifts in phospholipids and sphingolipids needed for membrane integrity, plasticity, and intracellular signaling. Future goals are to delineate WM abnormalities in AD using MALDI-IMS, and couple the findings with MRI-mass spectroscopy to improve in vivo diagnostics and early detection of brain biochemical responses to treatment.
Topics: Aldehydes; Analysis of Variance; Animals; Dinoprost; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Frontal Lobe; Lipid Metabolism; Male; Mice; Phospholipids; Principal Component Analysis; Protein Carbonylation; Smoking; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Substance Withdrawal Syndrome; White Matter
PubMed: 26836183
DOI: 10.3233/JAD-150916 -
Theriogenology Mar 2020The aim of the present study was to determine the recovery of embryonic structures (ova/embryos) and fertilization rate in superovulated buffaloes treated with PGF...
The aim of the present study was to determine the recovery of embryonic structures (ova/embryos) and fertilization rate in superovulated buffaloes treated with PGF during the periovulatory period. On day 0 (D0), buffaloes at random stages of the estrous cycle were treated with an intravaginal progesterone device (P4; 1.0 g) and estradiol benzoate (EB, 2.0 mg i.m.). From D4 to D7, all buffaloes received i.m. FSH (200 mg total) twice-daily over 4 days in decreasing doses. On D6 and D7, the animals were given PGF analogue (0.53 mg i.m. sodium cloprostenol) and the P4 device was removed on D7. On D8, all buffaloes received GnRH (20 μg i.m. buserelin acetate). Buffaloes were then randomly allocated to one of three groups: control (Group C, n = 18), no further treatment; PGF analogue injection (Group IM-PGF; n = 18), four injections (0.53 mg i.m. sodium cloprostenol) 12 h apart, from D8 to D10; PGF analogue osmotic pump (Group OP-PGF; n = 18), s.c. osmotic mini-pump (2.12 mg sodium cloprostenol) from D8 to D10. The study had a crossover design (three treatments x three replicates). All animals underwent timed AI, 12 and 24 h after treatment with GnRH. Embryonic structures were recovered on D14. Ovarian ultrasonography was used on D8 and D14 to record follicular superstimulation and superovulatory responses. Blood samples were obtained on Days 7, 8, 9 and 10 to measure circulating concentrations of P4, E2 and PGFM. Data were analyzed by GLIMMIX procedure of SAS®. There was no effect (P = 0.58) of treatment on the total number of embryonic structures (Group C, 2.1 ± 0.8; Group IM-PGF, 2.1 ± 0.6; Group OP-PGF, 1.4 ± 0.4). There was also no effect (P = 0.93) of treatment on the recovery rate of embryonic structures (oocytes and embryos D14/CL D14). The fertilization rate was higher (P = 0.04) in Groups IM-PGF (84.6%) and OP-PGF (88.0%), which did not differ, than Group C (63.2%). The viable embryos rate was greater (P < 0.01) for Groups IM-PGF (82.0%) and OP-PGF (88.0%) than Group C (52.6%). There was no interaction between treatment and time and treatment effects for P4, E2 and PGFM concentrations. The findings showed that treatment with PGF during the periovulatory period has potential to increase fertilization rate and embryo production in superovulated buffaloes.
Topics: Animals; Buffaloes; Dinoprost; Estradiol; Female; Fertility; Ovulation; Progesterone
PubMed: 31757482
DOI: 10.1016/j.theriogenology.2019.11.010 -
Scientific Reports Mar 2016Techniques to image lymphatic vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome...
Techniques to image lymphatic vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting lymphatic vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting lymphatic vessel function in mice, and to establish an in vivo system for evaluation of contractile agonists and antagonists using near-infrared fluorescence imaging. The flank collecting lymphatic vessel in mice was exposed using a surgical technique and a near-infrared tracer was infused into the inguinal lymph node. Collecting lymphatic vessel contractility and valve function could be easily visualized after the infusion. A diameter tracking method was established and the diameter of the vessel was found to closely correlate to near-infrared fluorescence signal. Phasic contractility measures of frequency and amplitude were established using an automated algorithm. The methods were validated by tracking the vessel response to topical application of a contractile agonist, prostaglandin F2α, and by demonstrating the potential of the technique for non-invasive evaluation of modifiers of lymphatic function. These new methods will enable high-resolution imaging and quantification of collecting lymphatic vessel function in animal models and may have future clinical applications.
Topics: Animals; Dinoprost; Humans; Lymph Nodes; Lymphatic Vessels; Mice; Optical Imaging
PubMed: 26960708
DOI: 10.1038/srep22930 -
Respiratory Medicine May 2009Collection of exhaled breath condensate (EBC) is a safe, non-invasive method to collect droplets of the airway surface liquid and measure mediators of airway... (Comparative Study)
Comparative Study
BACKGROUND
Collection of exhaled breath condensate (EBC) is a safe, non-invasive method to collect droplets of the airway surface liquid and measure mediators of airway inflammation and oxidative stress, such as cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane.
OBJECTIVE
The aim of our study was to investigate baseline values of inflammatory lipid mediators in EBC and their relation to asthma severity.
METHODS
Nineteen healthy subjects, 16 mild, 12 moderate and 15 severe asthmatics were studied. All subjects attended a clinic visit for spirometry and EBC collection. The concentrations of exhaled cys-LTs and 8-isoprostane were measured by means of specific enzyme immunoassays.
RESULTS
8-isoprostane levels were significantly increased in mild (49.1+/-5.2 pg/mL, p<0.001), moderate (49.7+/-5.2 pg/mL, p<0.001) and severe asthmatics (77.7+/-7.3 pg/mL, p<0.001), compared to healthy controls (16.4+/-1.6 pg/mL). Moreover, 8-isoprostane levels were significantly higher in severe compared to mild and moderate asthmatics (p<0.01). Cys-LT levels were significantly higher in moderate (34.6+/-4.4 pg/mL, p<0.05) and severe asthmatics (47.9+/-6.0 pg/mL, p<0.001), while no significant difference was found between healthy controls and mild asthmatics. 8-isoprostane levels in EBC of asthmatics strongly correlated with cys-LT levels (r=0.61, p<0.0001).
CONCLUSIONS
8-isoprostane and cys-LT are detectable in EBC of healthy subjects and their levels progressively increase in asthmatic patients according to disease severity. The correlation found between these two lipid mediators indicating a link between oxidative stress and airway inflammation.
Topics: Adult; Asthma; Breath Tests; Case-Control Studies; Cross-Sectional Studies; Cysteine; Dinoprost; Female; Forced Expiratory Volume; Greece; Humans; Immunoenzyme Techniques; Leukotrienes; Male; Middle Aged; Oxidative Stress; Spirometry
PubMed: 19110408
DOI: 10.1016/j.rmed.2008.11.009 -
The Journal of Reproduction and... Feb 2022The aim of the present study was to evaluate the effects of continuous administration of linoleic acid or linolenic acid into the intra-uterine horn, ipsilateral to the...
The aim of the present study was to evaluate the effects of continuous administration of linoleic acid or linolenic acid into the intra-uterine horn, ipsilateral to the corpus luteum, on the duration of the estrous cycle and plasma progesterone (P4) concentration. The effects of linoleic and linolenic acids on bovine uterine and luteal functions were also studied using a tissue culture system. Intra-uterine administration of linoleic or linolenic acid (5 mg/10 ml of each per day) in cows, between days 12 and 21, resulted in a prolonged estrous cycle compared to the average duration of the last one to three estrous cycles before administration in each group (P < 0.05). Moreover, plasma P4 concentration in cows treated with linoleic or linolenic acid was high between days 19 and 21 (linoleic acid), or on day 20 (linolenic acid), compared to that of the control cows (saline administration; P < 0.05 or lower). Both linoleic (500 µg/ml) and linolenic (5 and 500 µg/ml) acids stimulated prostaglandin (PG) E2 but inhibited PGF2α production by cultured endometrial tissue (P < 0.01), while P4 production by cultured luteal tissue was not affected. These findings suggest that both linoleic and linolenic acids support luteal P4 production by regulating endometrial PG production and, subsequently, prolonging the duration of the estrous cycle in cows.
Topics: Animals; Cattle; Corpus Luteum; Dinoprost; Estrous Cycle; Female; Linolenic Acids; Progesterone
PubMed: 34803128
DOI: 10.1262/jrd.2021-107 -
Thorax Jul 2009Previous studies have presented contradictory data concerning obstructive sleep apnoea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies have presented contradictory data concerning obstructive sleep apnoea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study was undertaken to (1) compare the concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma of middle-aged men with OSAS and no other known co-morbidity and healthy controls of the same age, gender and body mass index; and (2) test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy attenuates oxidative stress and nitrate deficiency.
METHODS
A prospective, randomised, placebo controlled, double-blind, crossover study was performed in 31 consecutive middle-aged men with newly diagnosed OSAS and 15 healthy control subjects. Patients with OSAS were randomised to receive sham CPAP or effective CPAP for 12 weeks. Blood pressure, urinary catecholamine levels and plasma 8-isoprostane and NOx concentrations were obtained before and after both treatment modalities.
RESULTS
Patients with OSAS had significantly higher 8-isoprostane levels (median (IQR) 42.5 (29.2-78.2) vs 20.0 (12.5-52.5) pg/ml, p = 0.041, Mann-Whitney test) and lower NOx levels (264 (165-650) vs 590 (251-1465) micromol/l, p = 0.022) than healthy subjects. Body mass index, blood pressure and urinary catecholamines were unchanged by CPAP therapy, but 8-isoprostane concentrations decreased (38.5 (24.2-58.7) pg/ml at baseline vs 22.5 (16.2-35.3) pg/ml on CPAP, p = 0.0001) and NOx levels increased (280 (177-707) vs 1373 (981-1517) micromol/l, p = 0.0001) after CPAP.
CONCLUSIONS
OSAS is associated with an increase in oxidative stress and a decrease in NOx that is normalised by CPAP therapy.
Topics: Adult; Aged; Blood Pressure; Continuous Positive Airway Pressure; Dinoprost; Double-Blind Method; Humans; Male; Middle Aged; Nitrates; Nitrites; Oxidative Stress; Prospective Studies; Sleep Apnea, Obstructive
PubMed: 19074930
DOI: 10.1136/thx.2008.100537 -
Acta Neurobiologiae Experimentalis 2010The study was aimed to examine the effect of chronic intermittent hypoxia (CIH) on spatial memory of growing rats and to explore the possible underlying mechanisms....
The study was aimed to examine the effect of chronic intermittent hypoxia (CIH) on spatial memory of growing rats and to explore the possible underlying mechanisms. Sixty two rats were trained to perform the 8-arm radial maze task and were divided into four groups: 2-week-CIH (2IH) 2-week-control (2C) 4-week-CIH (4IH) and 4-week-control (4C). There were more reference memory errors, working memory errors and total memory errors in 2IH and 4IH groups compared to the controls. The levels of 8-iso-Prostaglandin F(2-alpha) [8-ISO-PGF(2-alpha)] an in vivo marker for oxidative stress, in serum, hippocampus and prefrontal cortex were higher in CIH groups than the control groups. There were significant correlations between the levels of 8-ISO-PGF(2-alpha) and numbers of memory errors. The ultrastructural changes were evident in the hippocampal and prefrontal cortical tissues from the CIH groups. These results indicate that CIH can induce oxidative stress in brain tissues involved in spatial memory function.
Topics: Animals; Cell Hypoxia; Dinoprost; Hippocampus; Hydrogen Peroxide; Male; Maze Learning; Memory Disorders; Oxidative Stress; Prefrontal Cortex; Rats; Rats, Sprague-Dawley
PubMed: 20871647
DOI: 10.55782/ane-2010-1799 -
Short communication: Meta-analysis on therapy of bovine endometritis with prostaglandin F-An update.Journal of Dairy Science Nov 2018The objective of the study was to update a prior meta-analysis on the efficacy of the treatment of bovine endometritis with PGF. Clinical endometritis in cattle is... (Meta-Analysis)
Meta-Analysis
The objective of the study was to update a prior meta-analysis on the efficacy of the treatment of bovine endometritis with PGF. Clinical endometritis in cattle is defined as the presence of a purulent or mucopurulent vaginal discharge after 20 or 26 d, respectively, postpartum. Although the prevalence and impact of this disease are well known, the questions of whether and how to treat endometritis are still controversially discussed. Hence, to ensure timeliness of scientific results, we updated an existing meta-analysis published in 2013 that showed no treatment effect of PGF in cases of bovine endometritis. As in the prior meta-analysis, a comprehensive literature search was conducted. After applying specific inclusion and exclusion criteria, 3 trials remained that could be added to the 6 trials in the initial meta-analysis. Data for each trial were analyzed using the meta-analysis software Review Manager (version 5.3; The Nordic Cochrane Centre, Copenhagen, Denmark). Estimated effect sizes of PGF were calculated on calving to first service interval (CFSI) and calving to conception interval (CCI). As revealed by the initial meta-analysis, PGF treatment still had no effect on both reproductive parameters. Heterogeneity remained substantial for CFSI and CCI and even increased for CCI compared with the initial meta-analysis. Subgroup analysis, however, did not reveal a source of heterogeneity. In updating the meta-analysis, publication bias for trials reporting CCI became even more pronounced, suggesting that studies with higher standard error (i.e., usually smaller studies) that reported a prolonging effect on CCI after a PGF treatment were less likely to be published. Finally, although the number of trials published on the chosen topic and their comparability are still limited, this update of our meta-analysis now provides results that are based on approximately twice the number of included cows. The overall outcome, however, has not substantially changed and a positive effect of a PGF treatment in case of clinical endometritis could not be shown. Therefore, we do not recommend a treatment of bovine endometritis with PGF as a means to improve reproductive performance.
Topics: Animals; Cattle; Cattle Diseases; Dinoprost; Endometritis; Female; Postpartum Period; Reproduction
PubMed: 30172399
DOI: 10.3168/jds.2018-14933 -
Journal of the American Heart... Mar 2015Matrix metalloproteinase (MMP)-2 deficiency makes humans and mice susceptible to inflammation. Here, we reveal an MMP-2-mediated mechanism that modulates the...
BACKGROUND
Matrix metalloproteinase (MMP)-2 deficiency makes humans and mice susceptible to inflammation. Here, we reveal an MMP-2-mediated mechanism that modulates the inflammatory response via secretory phospholipase A2 (sPLA2), a phospholipid hydrolase that releases fatty acids, including precursors of eicosanoids.
METHODS AND RESULTS
Mmp2(-/-) (and, to a lesser extent, Mmp7(-/-) and Mmp9(-/-)) mice had between 10- and 1000-fold elevated sPLA2 activity in plasma and heart, increased eicosanoids and inflammatory markers (both in the liver and heart), and exacerbated lipopolysaccharide-induced fever, all of which were blunted by adenovirus-mediated MMP-2 overexpression and varespladib (pharmacological sPLA2 inhibitor). Moreover, Mmp2 deficiency caused sPLA2-mediated dysregulation of cardiac lipid metabolic gene expression. Compared with liver, kidney, and skeletal muscle, the heart was the single major source of the Ca(2+)-dependent, ≈20-kDa, varespladib-inhibitable sPLA2 that circulates when MMP-2 is deficient. PLA2G5, which is a major cardiac sPLA2 isoform, was proinflammatory when Mmp2 was deficient. Treatment of wild-type (Mmp2(+/+)) mice with doxycycline (to inhibit MMP-2) recapitulated the Mmp2(-/-) phenotype of increased cardiac sPLA2 activity, prostaglandin E2 levels, and inflammatory gene expression. Treatment with either indomethacin (to inhibit cyclooxygenase-dependent eicosanoid production) or varespladib (which inhibited eicosanoid production) triggered acute hypertension in Mmp2(-/-) mice, revealing their reliance on eicosanoids for blood pressure homeostasis.
CONCLUSIONS
A heart-centric MMP-2/sPLA2 axis may modulate blood pressure homeostasis, inflammatory and metabolic gene expression, and the severity of fever. This discovery helps researchers to understand the cardiovascular and systemic effects of MMP-2 inhibitors and suggests a disease mechanism for human MMP-2 gene deficiency.
Topics: Animals; Cell Line; Dinoprost; Dinoprostone; Fever; Gene Expression Regulation; Inflammation; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Phospholipases A2, Secretory; Polymerase Chain Reaction
PubMed: 25820137
DOI: 10.1161/JAHA.115.001868