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Respiratory Medicine 2021The purpose of this study was to investigate how 8-isoprostanes, used as a marker of airway oxidative stress, were related to sinus disease and asthma.
BACKGROUND
The purpose of this study was to investigate how 8-isoprostanes, used as a marker of airway oxidative stress, were related to sinus disease and asthma.
METHODS
We analyzed samples and data from two separate studies, one investigating sinonasal disease in asthma, the other investigating the effect of BMI on airway disease. We measured airway (nasal lavage) 8-isoprostanes and investigated the relationship with measures of sinus and asthma symptoms, asthma control and lung function.
RESULTS
The study of people with sinonasal disease and poorly controlled asthma included 48 obese, 31 overweight and 23 lean participants. In multivariate analysis, nasal lavage 8-isoprostane levels increased with increasing BMI (p < 0.01), and were higher in Caucasian than African American participants (p = 0.01). Sinus symptoms were inversely related to nasal 8-isoprostanes (p = 0.02) independent of BMI and Race. In the study investigating the effect of BMI on airway disease, we enrolled 13 controls with obesity and 21 people with obesity and asthma: 8-isoprostane levels were higher in obese controls than in obese people with asthma (p < 0.01), and levels were inversely related to sinus symptoms (p = 0.02) and asthma control (p < 0.01).
INTERPRETATION
8-isoprostanes in nasal lavage are increased in obesity, and increased in Caucasians compared with African Americans. However, levels are higher in obese controls than obese people with asthma, and appear inversely related to symptoms of airway disease.
CLINICAL IMPLICATION
Airway 8-isoprostanes likely reflect complex oxidative signaling pathways, which are altered in obesity and those of different race, rather than being a simple marker of airway oxidative injury.
CAPSULE SUMMARY
Increased airway oxidative signaling (8-isoprostanes), may reflect normal physiology in the setting of obesity, as decreased levels are associated with disease activity in people with chronic sinonasal disease and asthma.
Topics: Adult; Asthma; Biomarkers; Body Mass Index; Dinoprost; Female; Humans; Male; Middle Aged; Nasal Lavage Fluid; Obesity; Oxidative Stress; Paranasal Sinus Diseases; Racial Groups; Young Adult
PubMed: 34166960
DOI: 10.1016/j.rmed.2021.106506 -
ACS Chemical Neuroscience Apr 2016The neuroinflammatory response has received increasing attention as a key factor in the pathogenesis of Alzheimer's disease (AD). Microglia, the innate immune cells and... (Review)
Review
The neuroinflammatory response has received increasing attention as a key factor in the pathogenesis of Alzheimer's disease (AD). Microglia, the innate immune cells and resident phagocytes of the brain, respond to accumulating Aβ peptides by generating a nonresolving inflammatory response. While this response can clear Aβ peptides from the nervous system in some settings, its failure to do so in AD accelerates synaptic injury, neuronal loss, and cognitive decline. The complex molecular components of this response are beginning to be unraveled, with identification of both damaging and protective roles for individual components of the neuroinflammatory response. Even within one molecular pathway, contrasting effects are often present. As one example, recent studies of the inflammatory cyclooxygenase-prostaglandin pathway have revealed both beneficial and detrimental effects dependent on the disease context, cell type, and downstream signaling pathway. Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenases, are associated with reduced AD risk when taken by cognitively normal populations, but additional clinical and mouse model studies have added complexities and caveats to this finding. Downstream of cyclooxygenase activity, prostaglandin E2 signaling exerts both damaging pro-inflammatory and protective anti-inflammatory effects through actions of specific E-prostanoid G-protein coupled receptors on specific cell types. These complexities underscore the need for careful study of individual components of the neuroinflammatory response to better understand their contribution to AD pathogenesis and progression.
Topics: Alzheimer Disease; Animals; Dinoprost; Encephalitis; Humans; Microglia; Signal Transduction
PubMed: 26979823
DOI: 10.1021/acschemneuro.6b00016 -
Cells Jun 2022Fatty liver, characterized by excessive lipid droplet (LD) accumulation in hepatocytes, is a common physiological condition in humans and aquaculture species. Lipid...
Fatty liver, characterized by excessive lipid droplet (LD) accumulation in hepatocytes, is a common physiological condition in humans and aquaculture species. Lipid mobilization is an important strategy for modulating the number and size of cellular LDs. Cyclooxygenase (COX)-mediated arachidonic acid derivatives are known to improve lipid catabolism in fish; however, the specific derivatives remain unknown. In the present study, we showed that serum starvation induced LD degradation via autophagy, lipolysis, and mitochondrial energy production in zebrafish hepatocytes, accompanied by activation of the COX pathway. The cellular concentration of PGF2α, but not other prostaglandins, was significantly increased. Administration of a COX inhibitor or interference with PGF2α synthase abolished serum deprivation-induced LD suppression, LD-lysosome colocalization, and expression of autophagic genes. Additionally, exogenous PGF2α suppressed the accumulation of LDs, promoted the accumulation of lysosomes with LD and the autophagy marker protein LC3A/B, and augmented the expression of autophagic genes. Moreover, PGF2α enhanced mitochondrial accumulation and ATP production, and increased the transcript levels of β-oxidation- and mitochondrial respiratory chain-related genes. Collectively, these findings demonstrate that the COX pathway is implicated in lipid degradation induced by energy deprivation, and that PGF2α is a key molecule triggering autophagy, lipolysis, and mitochondrial development in zebrafish hepatocytes.
Topics: Animals; Autophagy; Dinoprost; Hepatocytes; Lipid Droplets; Prostaglandins; Zebrafish
PubMed: 35740999
DOI: 10.3390/cells11121870 -
Journal of Breath Research Feb 2017We aimed to assess the evidence for the use of 8-isoprostane in exhaled breath condensate (EBC) as a biomarker in adult asthma. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We aimed to assess the evidence for the use of 8-isoprostane in exhaled breath condensate (EBC) as a biomarker in adult asthma.
DESIGN
A systematic review and meta-analysis of EBC 8-isoprostane.
METHODS
We searched a number of online databases (including PubMed, Embase and Scopus) in January 2016. We included studies of adult non-smokers with EBC collection and asthma diagnosis conducted according to recognised guidelines. We aimed to pool data using random effects meta-analysis and assess heterogeneity using I .
RESULTS
We included twenty studies, the findings from which were inconsistent. Seven studies (n = 329) reported 8-isoprostane levels in asthma to be significantly higher than that of control groups, whilst six studies (n = 403) did not. Only four studies were appropriate for inclusion in a random effects meta-analysis of mean difference. This found a statistically significant between-groups difference of 22 pg ml. Confidence in the result is limited by the small number of studies and by substantial statistical heterogeneity (I = 94).
CONCLUSION
The clinical value of EBC 8-isoprostane as a quantitative assessment of oxidative stress in asthma remains unclear due to variability in results and methodological heterogeneity. It is essential to develop a robust and standardised methodology if the use of EBC 8-isoprostane in asthma is to be properly evaluated.
Topics: Adult; Asthma; Biomarkers; Breath Tests; Case-Control Studies; Dinoprost; Exhalation; Humans
PubMed: 28102831
DOI: 10.1088/1752-7163/aa5a8a -
Reproductive Biology and Endocrinology... Nov 2003There is clear evidence for intraluteal production of prostaglandins (PGs) in numerous species and under a variety of experimental conditions. In general, secretion of... (Review)
Review
There is clear evidence for intraluteal production of prostaglandins (PGs) in numerous species and under a variety of experimental conditions. In general, secretion of PGs appears to be elevated in the early corpus luteum (CL) and during the period of luteolysis. Regulation of intraluteal PG production is regulated by a variety of factors. An autoamplification pathway in which PGF-2alpha stimulates intraluteal production of PGF-2alpha has been identified in a number of species. The mechanisms underlying this autoamplification pathway appear to differ by species with expression of Cyclooxygenase-2 (Cox-2) and activity of phospholipase A2 acting as important physiological control points. In addition, a number of other responses that are induced by PGF-2alpha (decreased luteal progesterone, increased endothelin-1, increased cytokines) also have been found to increase intraluteal PGF-2alpha production. Thus, regulation of intraluteal PG production may serve to initiate or amplify physiological signals to the CL and may be important in specific aspects of luteal physiology particularly during luteal regression.
Topics: Animals; Corpus Luteum; Dinoprost; Female; Humans; Luteal Phase; Prostaglandins
PubMed: 14613533
DOI: 10.1186/1477-7827-1-91 -
Molecules and Cells Nov 2010Oxidative stress and inflammation are supposed to be the key players of several acute and chronic diseases, and also for progressive aging process. Eicosanoids,... (Review)
Review
Oxidative stress and inflammation are supposed to be the key players of several acute and chronic diseases, and also for progressive aging process. Eicosanoids, especially prostaglandin F(2α) (PGF(2α)) and F₂-isoprostanes are endogenous compounds that are involved both in physiology and the above mentioned pathologies. These compounds are biosynthesized mainly from esterified arachidonic acid through both enzymatic and non-enzymatic free radical-catalysed reactions in vivo, respectively. They have shown to possess potent biological activities in addition to their application as biomarkers of oxidative stress and inflammation. Recent advancement of methodologies has made it possible to quantify these compounds more reliably and apply them in various in vivo studies successfully. Today, experimental and clinical studies have revealed that both PGF(2α) and F₂-isoprostanes are involved in severe acute or chronic inflammatory conditions such as rheumatic diseases, asthma, risk factors of atherosclerosis, diabetes, ischemia-reperfusion, septic shock and many others. These evidences promote that assessment of bioactive PGF(2α) and F₂-isoprostanes simultaneously in body fluids offers unique non-invasive analytical opportunity to study the function of these eicosanoids in physiology, oxidative stress-related and inflammatory diseases, and also in the determination of potency of various radical scavengers, anti-inflammatory compounds, drugs, antioxidants and diet.
Topics: Animals; Dinoprost; F2-Isoprostanes; Humans; Inflammation; Oxidative Stress
PubMed: 21113821
DOI: 10.1007/s10059-010-0157-1 -
International Journal of Environmental... May 2020Bisphenols, particularly bisphenol A (4,4'-(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with... (Review)
Review
Bisphenols, particularly bisphenol A (4,4'-(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with adverse health outcomes. We investigated the associations between exposure to bisphenols and biomarkers of oxidative stress in human studies over the last 12 years (2008‒2019) related to six health endpoints and evaluated their suitability as effect biomarkers. database searches identified 27 relevant articles that were used for data extraction. In all studies, BPA exposure was reported, whereas some studies also reported other bisphenols. More than a dozen different biomarkers were measured. The most frequently measured biomarkers were 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoprostane) and malondialdehyde (MDA), which almost always were positively associated with BPA. Methodological issues were reported for MDA, mainly the need to handle samples with caution to avoid artefact formation and its measurements using a chromatographic step to distinguish it from similar aldehydes, making some of the MDA results less reliable. Urinary 8-OHdG and 8-isoprostane can be considered the most reliable biomarkers of oxidative stress associated with BPA exposure. Although none of the biomarkers are considered BPA- or organ-specific, the biomarkers can be assessed repeatedly and non-invasively in urine and could help to understand causal relationships.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Biomarkers; Child; Cross-Sectional Studies; Dinoprost; Female; Follow-Up Studies; Humans; Infant, Newborn; Male; Oxidative Stress; Phenols; Pregnancy; Prospective Studies; Single-Blind Method; Young Adult
PubMed: 32455625
DOI: 10.3390/ijerph17103609 -
Organic Letters Dec 2022We report a general, catalyst-controlled route to prostaglandin F2 and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki-Miyaura coupling...
We report a general, catalyst-controlled route to prostaglandin F2 and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki-Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji-Trost alkylation and iodolactonization. The synthesis of PG F2 was achieved in 19% yield in 16 longest linear steps.
Topics: Dinoprost; Catalysis
PubMed: 36446080
DOI: 10.1021/acs.orglett.2c03718 -
The Journal of Reproduction and... Apr 2022Prostaglandin F (PGF) and its analogs are used to induce luteolysis in estrus synchronization programs to terminate unwanted pregnancies or to promote ovulation in... (Review)
Review
Prostaglandin F (PGF) and its analogs are used to induce luteolysis in estrus synchronization programs to terminate unwanted pregnancies or to promote ovulation in certain cow subpopulations. In the past few decades, the luteolytic dose of PGF has remained unchanged. This review explores the clinical implications of increasing the standard dose for these applications in high-producing dairy cows. Ultrasonography may assist in selecting the most appropriate PGF dose and improve the results. A reference has been used for PGF for promoting ovulation in herds showing poor reproductive performance.
Topics: Animals; Cattle; Dinoprost; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Lactation; Ovulation; Pregnancy; Progesterone; Prostaglandins F
PubMed: 34980770
DOI: 10.1262/jrd.2021-119 -
Theriogenology Sep 2021Although prostaglandins are important in the ovulation process, a precise role for prostaglandin F2α (PGF) has not been elucidated. This study aimed to evaluate the...
Although prostaglandins are important in the ovulation process, a precise role for prostaglandin F2α (PGF) has not been elucidated. This study aimed to evaluate the regulation of PGF receptor mRNA (PTGFR) in granulosa cells and the local effect of PGF on ovulation and luteinization. In Experiment 1, using samples collected in vivo before (Day 2), during (Day 3) and after (Day 4) follicular deviation, expression of PTGFR in bovine granulosa cells was more abundant in the dominant follicle after deviation than in subordinates (P < 0.05). However, the expression of PTGFR was not regulated (P = 0.1) in preovulatory follicles at different time-points (0, 3, 6, 12 and 24 h) after ovulation induction with GnRH. In Experiment 2, to assess the role of systemic PGF treatment on luteinization and vascularization of preovulatory follicles, flunixin meglumine (FM), a nonsteroidal anti-inflammatory drug, was used to inhibit endogenous prostaglandin synthesis. Cows with preovulatory follicles were induced to ovulate with GnRH (0 h) and allocated to three groups: Control, with no further treatment; FM, treated with 2.2 mg/kg FM im 17 h after GnRH treatment; and FM + PGF, treated with FM 17 h after GnRH, followed by 25 mg dinoprost tromethamine (PGF) 23 h after GnRH treatment. FM injection was able to reduce the concentration of PGF in the follicular fluid (FF) (P < 0.001). However, contrary to our hypothesis, color Doppler ultrasound evaluations revealed decreased vascular flow in FM + PGF group (P < 0.05), and no effect of the treatments on intrafollicular P4 and E2 concentrations 24 h after GnRH. The prostaglandin metabolite (PGFM) concentrations in the FF were greater in cows receiving systemic PGF (P < 0.001), which prompted us to further check its role on ovulation. Therefore, in Experiment 3, in a final attempt to demonstrate the local effect of PGF on ovulation, cows with preovulatory follicles received an intrafollicular injection (IFI) of PBS (Control) or 100 ng/mL purified PGF (PGF group). PGF treatment did not affect the time of ovulation after IFI (66 ± 6.4 and 63 ± 8.5 h for control and PGF, respectively; P > 0.05), further suggesting that it has no direct effect in the ovulatory process. Based on our findings, we concluded that FM decreased PGF synthesis within the follicle, whereas PGF treatment decreased follicular vascularization. In addition, the in vivo model of intrafollicular injection evidenced that PGF alone is not able to locally induce ovulation.
Topics: Animals; Cattle; Dinoprost; Female; Gonadotropin-Releasing Hormone; Luteinization; Ovarian Follicle; Ovulation; Progesterone
PubMed: 34004368
DOI: 10.1016/j.theriogenology.2021.05.008