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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 -
FEBS Letters May 1998Tritium labelled (x=1.1 MBq/17.7 microg/kg) and unlabelled 8-iso-PGF2alpha (43 microg/kg) were administered intravenously to female rabbits and frequent blood and...
Tritium labelled (x=1.1 MBq/17.7 microg/kg) and unlabelled 8-iso-PGF2alpha (43 microg/kg) were administered intravenously to female rabbits and frequent blood and continuous urinary samples were collected up to 4 h. The total radioactivity was lost rapidly from the circulation. About 80% of the total radioactivity was found in urine within 4 h. The plasma half-life of 8-iso-PGF2alpha is found to be 1 min at the distribution phase. The terminal elimination phase half-life was about 4 min. At 1.5 min after administration 64%, 19% and 13% of the plasma radioactivity represented 8-iso-PGF2alpha, 15-keto-8-iso-PGF2alpha and beta-oxidised products, respectively. The values for 20-min plasma were 5%, 2%, and 88%. The radiochromatograms from 10 min-4 h urinary samples were dominated by more polar beta-oxidised products. Alpha-Tetranor-15-keto-13,14-dihydro-8-iso-PGF2alpha was identified as a major urinary metabolite.Thus, 8-iso-PGF2alpha metabolises in the rabbit mainly to several degraded polar metabolites through dehydrogenation at C-15, reduction of delta13-double bond and beta-oxidation, and excretes efficiently into the urine.
Topics: Animals; Chromatography, High Pressure Liquid; Dinoprost; F2-Isoprostanes; Female; Isotope Labeling; Oxidation-Reduction; Rabbits; Tritium
PubMed: 9645469
DOI: 10.1016/s0014-5793(98)00481-5 -
Medicine Feb 2019This study aims to investigate the correlation between oxidative stress and intra-abdominal fat (IAF) in obese young and middle-aged males.The present study included 136... (Observational Study)
Observational Study
This study aims to investigate the correlation between oxidative stress and intra-abdominal fat (IAF) in obese young and middle-aged males.The present study included 136 male examinees in the Examination Center of the First Hospital of Qinhuangdao from October 10, 2015 to December 10, 2015. Then, clinical data, oxidative stress indices (8-iso-prostaglandin F2α [8-iso-PGF2α], malondialdehyde [MDA], and superoxide dismutase [SOD]), and IAF area were recorded. All subjects were assigned into 3 groups according to body mass index (BMI): obese group (BMI ≥ 28 kg/m, 43 subjects), overweight group (24 ≤ BMI < 28 kg/m, 46 subjects), and control group (BMI < 24 kg/m, 47 subjects). Then, statistical analysis was performed.There were significant differences in IAF area, leptin, adiponectin, 8-iso-PGF2α, MDA, SOD, fasting insulin (FINS), fasting blood glucose (FBG), and homeostasis model assessment-insulin resistance (HOMA-IR) among these 3 groups (P < .05). Male subjects in the obese group had higher leptin, 8-iso-PGF2α, MDA, FINS, and HOMA-IR levels, compared to subjects in the overweight and control groups. Furthermore, subjects in the overweight group had a larger IAF area and higher 8-iso-PGF2α, MDA, and FBG levels, when compared to controls. In addition, SOD was significantly lower in the obese and overweight groups than in the control group. However, there were no statistical differences in age, systolic and diastolic blood pressure, lipids, and islet β-cell secretion function (homeostasis model assessment-β) among these 3 groups (P ≥ .05). Moreover, the IAF area was positively correlated to 8-iso-PGF2α and MDA, and negatively correlated to SOD.Oxidative stress is significantly associated with the IAF area in obese males, and abdominal obesity could increase oxidative stress level and insulin resistance.
Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Dinoprost; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Malondialdehyde; Middle Aged; Obesity; Oxidative Stress; Superoxide Dismutase; Young Adult
PubMed: 30762765
DOI: 10.1097/MD.0000000000014469 -
American Journal of Physiology.... Mar 2000The objectives of this study were to assess oxidant damage during and after spaceflight and to compare the results against bed rest with 6 degrees head-down tilt. We...
The objectives of this study were to assess oxidant damage during and after spaceflight and to compare the results against bed rest with 6 degrees head-down tilt. We measured the urinary excretion of the F(2) isoprostane, 8-iso-prostaglandin (PG) F(2alpha), and 8-oxo-7,8-dihydro-2 deoxyguanosine (8-OH DG) before, during, and after long-duration spaceflight (4-9 mo) on the Russian space station MIR, short-duration spaceflight on the shuttle, and 17 days of bed rest. Sample collections on MIR were obtained between 88 and 186 days in orbit. 8-iso-PGF(2alpha) and 8-OH DG are markers for oxidative damage to membrane lipids and DNA, respectively. Data are mean +/- SE. On MIR, isoprostane levels were decreased inflight (96. 9 +/- 11.6 vs. 76.7 +/- 14.9 ng. kg(-1). day(-1), P < 0.05, n = 6) due to decreased dietary intake secondary to impaired thermoregulation. Isoprostane excretion was increased postflight (245.7 +/- 55.8 ng. kg(-1). day(-1), P < 0.01). 8-OH DG excretion was unchanged with spaceflight and increased postflight (269 +/- 84 vs 442 +/- 180 ng. kg(-1). day(-1), P < 0.05). On the shuttle, 8-OH DG excretion was unchanged in- and postflight, but 8-iso-PGF(2alpha) excretion was decreased inflight (15.6 +/- 4.3 vs 8.0 +/- 2.7 ng. kg(-1). day(-1), P < 0.05). No changes were found with bed rest, but 8-iso-PGF(2alpha) was increased during the recovery phase (48.9 +/- 23.0 vs 65.4 +/- 28.3 ng. kg(-1). day(-1), P < 0.05). The changes in isoprostane production were attributed to decreased production of oxygen radicals from the electron transport chain due to the reduced energy intake inflight. The postflight increases in the excretion of the products of oxidative damage were attributed to a combination of an increase in metabolic activity and the loss of some host antioxidant defenses inflight. We conclude that 1) oxidative damage was decreased inflight, and 2) oxidative damage was increased postflight.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Bed Rest; Deoxyguanosine; Dinoprost; Energy Intake; F2-Isoprostanes; Head-Down Tilt; Humans; Oxidants; Space Flight
PubMed: 10710490
DOI: 10.1152/ajpendo.2000.278.3.E375 -
The Journal of Reproduction and... Feb 2021Over the past few decades, the luteolytic dose of prostaglandin F (PGF) and its analogs, used to synchronize estrus for fixed-time insemination in dairy cattle, have... (Review)
Review
Over the past few decades, the luteolytic dose of prostaglandin F (PGF) and its analogs, used to synchronize estrus for fixed-time insemination in dairy cattle, have remained unchanged. Given the beneficial effects of PGF on a young corpus luteum and on multiple ovulations in a fixed-time insemination protocol, and its therapeutic abortive effects on multiple ovulations in pregnant cows, we propose the use of a double PGF dose or two PGF treatments 24 hours apart. Ultrasonography procedures serve to identify luteal structures and may therefore help to determine the best PGF dose to improve the fertility of high-producing dairy cows.
Topics: Animals; Cattle; Dairying; Dinoprost; Dose-Response Relationship, Drug; Drug Administration Schedule; Estrus Synchronization; Female; Insemination, Artificial; Luteolysis; Pregnancy
PubMed: 33162429
DOI: 10.1262/jrd.2020-101 -
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 -
Circulation Journal : Official Journal... Feb 2018The gastroepiploic artery (GEA) plays an important role in the era of multiple arterial revascularization, but spasm is a major matter of concern. The internal thoracic...
BACKGROUND
The gastroepiploic artery (GEA) plays an important role in the era of multiple arterial revascularization, but spasm is a major matter of concern. The internal thoracic artery has been shown to have a strong tendency to spasm in its distal bifurcating part, whereas the segmental difference in vasoreactivity of the GEA has never been performed.Methods and Results:The full length of the GEA obtained from 21 patients undergoing a total gastrectomy was divided into 3 sections: proximal (5 cm from the origin), middle, and distal (5 cm from the end). Concentration-response curves for vasoconstrictors (phenylephrine, prostaglandin F2α, and endothelin-1) and vasodilators (carperitide, nitroglycerin, and nifedipine) were then established using organ baths. All the vasoconstrictors and vasodilators produced concentration-dependent responses in each section. As the concentration of the vasoconstrictors increased, segments at the distal section showed a significantly greater contraction than those at the middle and proximal sections regardless of the type of vasoconstrictor. The effective concentration of drugs that caused 50% of the maximal response for endothelin-1 was significantly greater in the distal section than that in the proximal sections. No significant difference was found in vasodilators-induced relaxation.
CONCLUSIONS
The contractility increases toward to the end of the GEA. Clinically, the distal portion of the GEA should be trimmed off and not be used as an anastomotic site wherever possible.
Topics: Dinoprost; Dose-Response Relationship, Drug; Endothelin-1; Gastroepiploic Artery; Humans; Phenylephrine; Vasoconstriction; Vasoconstrictor Agents
PubMed: 29238009
DOI: 10.1253/circj.CJ-17-0943 -
The Journal of Nutrition Jan 2018Diets with a high glycemic index (GI) and glycemic load (GL) have been hypothesized to increase oxidative stress, but the limited human studies are inconsistent.
BACKGROUND
Diets with a high glycemic index (GI) and glycemic load (GL) have been hypothesized to increase oxidative stress, but the limited human studies are inconsistent.
OBJECTIVE
The aim of this cross-sectional study was to investigate associations between dietary GI, GL, and carbohydrate intake and oxidative stress, as measured by F2-isoprostanes (F2-IsoPs).
METHODS
Concentrations of F2-IsoP and its metabolite (15-F2t-IsoP-M) were measured in urine samples collected at enrollment from 866 premenopausal women (aged 35-54 y) participating in the Sister Study. Total carbohydrate intake and dietary GI and GL were assessed using a validated food frequency questionnaire. Urinary F2-IsoP and 15-F2t-IsoP-M concentrations were compared across quintiles of carbohydrate intake, GI, and GL using multivariable linear regression models.
RESULTS
Urinary F2-IsoP concentrations were positively associated with dietary GI (P-trend = 0.023), and both F2-IsoP and 15-F2t-IsoP-M concentrations were positively associated with GL (F2-IsoP: P-trend < 0.001; 15-F2t-IsoP-M: P-trend < 0.001) and total carbohydrate intake (F2-IsoP: P-trend = 0.012; 15-F2t-IsoP-M: P-trend < 0.001). Stratified analyses suggested that a positive association between GI and urinary 15-F2t-IsoP-M concentrations was present among women with a body mass index [BMI (in kg/m2)] ≥30.0, but not among those with a BMI of <25.0 or 25.0-29.9 (P-interaction = 0.01).
CONCLUSIONS
Our cross-sectional analyses in a sample of premenopausal women support hypothesized relations between high dietary GI and GL and oxidative stress, as assessed by urinary F2-IsoP and 15-F2t-IsoP-M concentrations. Given potential associations between oxidative stress and the development of cardiovascular disease and type 2 diabetes, our findings may have important implications for reducing chronic disease risk.
Topics: Adult; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Diet; Dietary Carbohydrates; Dinoprost; F2-Isoprostanes; Female; Glycemic Index; Glycemic Load; Humans; Middle Aged; Nutrition Assessment; Oxidative Stress; Premenopause; Socioeconomic Factors; Surveys and Questionnaires
PubMed: 29378036
DOI: 10.1093/jn/nxx022 -
Veterinary Medicine and Science Nov 2018Persistent mating-induced endometritis (PMIE) is a significant cause of mare infertility hence its treatment would advance the management of susceptible mares....
Persistent mating-induced endometritis (PMIE) is a significant cause of mare infertility hence its treatment would advance the management of susceptible mares. Preimplantation factor (PIF) is secreted by viable embryos, including human, mouse and cattle, and is essential for maternal immune-tolerance without immune-suppression by modulating inflammation. This preliminary study aimed to test whether PIF exerts inflammatory-modulating properties upon equine endometrium challenged with Escherichia coli-derived lipopolysaccharide (LPS) using endometrial explant culture. Follicular (n = 3), luteal (n = 4), anoestrous (n = 4) and transitional (n = 4) stage endometrial explants were established and cultured in triplicate in either serum-free medium alone (control) or medium with; 50 or 100 nmol/L synthetic PIF (sPIF); 3 μg/mL LPS; LPS and 50 or 100 nmol/L sPIF; or scrambled PIF (PIFscr; same amino acid composition arranged in a different order). Media samples were collected at 24 and 72 h, representing acute and chronic inflammatory response. Radioimmunoassay determined Prostaglandin F (PGF ) as an inflammatory marker. The only significant observation was the abrogation of PGF response to LPS challenge by 100 nmol/L PIF for follicular stage tissue, 24 h after treatment. Further studies are therefore, warranted to realise PIF potential in managing PMIE.
Topics: Animals; Dinoprost; Endometrium; Female; Horses; Inflammation; Pregnancy Proteins; Tissue Culture Techniques
PubMed: 30273998
DOI: 10.1002/vms3.126 -
Frontiers in Endocrinology 2021Oxytocin (OT) is a crucial regulator of reproductive behaviors, including parturition in mammals. Arg-vasopressin (AVP) is a nonapeptide homologous to Arg-vasotocin...
Oxytocin (OT) is a crucial regulator of reproductive behaviors, including parturition in mammals. Arg-vasopressin (AVP) is a nonapeptide homologous to Arg-vasotocin (AVT) in teleosts that has comparable affinity for the OT receptor. In the present study, ovoviviparous guppies () were used to study the effect of AVT on delivery mediated by the activation of prostaglandin (PG) biosynthesis isotocin (IT) receptors (ITRs). One copy each of and and two copies of were identified in guppies. The results of the affinity assay showed that various concentrations of AVT and IT (10, 10, and 10 mol/L) significantly activated (P < 0.05). experiments revealed significant upregulation (P < 0.05) of cyclooxygenase 2 (), which is the rate-limiting enzyme involved in PG biosynthesis, and by AVT and IT. Furthermore, dual hybridization detected positive signals for and at the same site, implying that ITR1 may regulate gene expression. Measurement of prostaglandin F (PGF) concentrations showed that AVT induced PGF synthesis (P < 0.05) and that the effect of IT was not significant. Finally, intraperitoneal administration of PGF significantly induced premature parturition of guppies. This study is the first to identify and characterize AVT and ITRs in guppies. The findings suggest that AVT promotes PG biosynthesis ITR and that PGF induces delivery behavior in ovoviviparous guppies.
Topics: Animals; Behavior, Animal; Cyclooxygenase 2; Dinoprost; Oxytocin; Parturition; Poecilia; Receptors, Vasopressin; Up-Regulation; Vasotocin
PubMed: 33967951
DOI: 10.3389/fendo.2021.617580