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PloS One 2013It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but epidemiological evidence is limited. In the present...
It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but epidemiological evidence is limited. In the present study we evaluated the association between urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal study of older persons (aged 70-79 years). The present analyses was based on a subsample of 1027 men and 948 women free of mobility disability. Urinary concentration of 8-iso-PGF2α was measured by radioimmunoassay methods and adjusted for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men presented higher urinary concentrations of 8-iso-PGF2α than non-depressed men even after adjustment for multiple sociodemographic, lifestyle and health factors (p = 0.03, Cohen's d = 0.30). This association was not present in women (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in older men from a large sample of the general population. Further studies are needed to explore whether the modulation of oxidative stress may break down the link between late-life depression and its deleterious health consequences.
Topics: Aged; Depression; Dinoprost; Female; Humans; Lipid Peroxidation; Male; Sex Factors
PubMed: 23776478
DOI: 10.1371/journal.pone.0065406 -
Basic & Clinical Pharmacology &... Sep 2018Retinal arachidonic acid (ARA) levels in form-deprived eyes decline in guinea pigs. As prostaglandin F2α (PGF2α) is an ARA metabolite and endogenous agonist of...
Retinal arachidonic acid (ARA) levels in form-deprived eyes decline in guinea pigs. As prostaglandin F2α (PGF2α) is an ARA metabolite and endogenous agonist of prostaglandin F receptor (FP), we have been suggested that down-regulation of PGF2α-FP receptor signalling pathway contributes to myopia onset. To test this hypothesis, this study determines whether: (i) retinal PGF2α levels decline during the development of form deprivation myopia (FDM) in guinea pigs; (ii) FP receptor agonism and antagonism alter emmetropization and myopia development. Pigmented guinea pigs were randomly assigned to normal vision and form-deprived groups. Ultraperformance liquid chromatography coupled with a mass spectrometer (UPLC-MS) measured retinal PGF2α levels 2 weeks after form deprivation (FD). The selective FP agonist, latanoprost acid (LAT) and its corresponding antagonist, AL8810, were peribulbarly injected into each group. An eccentric infrared photorefractor (EIR) monitored refraction. A-scan ultrasonography measured axial elongation (AL) and vitreous chamber depth (VCD). Tonometry measured the intraocular pressure (IOP). Retinal PGF2α levels declined in form-deprived eyes compared to those in normal eyes. Neither LAT nor AL8810 affected IOP with or without FD. On the other hand, after 4 weeks of daily 0.5 μg AL8810 treatment, a myopia of -1.99 ± 0.34 dioptre (D) developed, but LAT had no effect on emmetropization in a normal visual environment. Nevertheless, daily 30 μg LAT treatment for 4 weeks inhibited FDM development by 41% (vehicle control: -8.39 ± 0.45 D; LAT: -4.95 ± 0.39 D; two-way anova with repeated measures, p < 0.05). Down-regulation of PGF2α-FP receptor signalling pathway may contribute to myopia onset as retinal PGF2α declined in myopic eyes and antagonism of FP receptor by AL8810 induced a myopic shift in normal vision environment. Meanwhile, up-regulation of this pathway by LAT inhibited FDM development. However, the mechanism underlying LAT-induced FDM inhibition needs further clarification. This uncertainty exists because its inhibition of FDM suggests that LAT strengthens the scleral framework which reduces axial elongation. On the other hand, its IOP-lowering effect is attributed to thinning and weakening the scleral framework in glaucoma treatment.
Topics: Animals; Arachidonic Acid; Chromatography, High Pressure Liquid; Dinoprost; Disease Models, Animal; Down-Regulation; Guinea Pigs; Intraocular Pressure; Latanoprost; Mass Spectrometry; Myopia; Prostaglandins F, Synthetic; Receptors, Prostaglandin; Retina; Signal Transduction; Tonometry, Ocular; Up-Regulation
PubMed: 29604230
DOI: 10.1111/bcpt.13017 -
PloS One 2020Prostaglandin F2 alpha (PGF2α) analogues such as latanoprost are common first-line intraocular pressure (IOP) lowering medications. However, their clinical use is...
Prostaglandin F2 alpha (PGF2α) analogues such as latanoprost are common first-line intraocular pressure (IOP) lowering medications. However, their clinical use is limited in some patient populations due to minimal or no IOP lowering response or side effects. In searching for a more targeted approach for IOP reduction, our lab recently identified Stanniocalcin-1 (STC-1) as a molecule that was required for latanoprost-mediated IOP reduction and also acted as a stand-alone IOP lowering agent. In order to determine whether latanoprost and STC-1 were equivalent and/or additive for IOP reduction, we treated C57BL/6J mice with one or a combination of these agents and measured IOP. Importance of the FP receptor for latanoprost- and STC-1-mediated IOP reduction was examined in C57BL/6J mice utilizing the pharmacologic FP receptor inhibitor AL-8810 as well as FP receptor knockout mice generated in our laboratory. Latanoprost-free acid (LFA) and STC-1 reduced IOP to a similar degree and were non-additive in C57BL/6J mice. As expected, the IOP lowering effects of LFA were abrogated by pharmacologic inhibition of the FP receptor with AL-8810 and in FP receptor knockout mice. In contrast, STC-1 maintained IOP-lowering effects in the presence of AL-8810 and also in FP receptor knockout mice. These results suggest that LFA and STC-1 show equivalent and non-additive IOP reduction in C57BL/6J mice and that unlike LFA, STC-1-mediated IOP reduction occurs independent of the FP receptor.
Topics: Animals; Dinoprost; Female; Genotype; Glycoproteins; Homozygote; Intraocular Pressure; Latanoprost; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Prostaglandin; Signal Transduction
PubMed: 32365129
DOI: 10.1371/journal.pone.0232591 -
International Journal of Molecular... Jun 2019Occupational exposure to wood dust has been estimated to affect 3.6 million workers within the European Union (EU). The most serious health effect caused by wood dust is...
Occupational exposure to wood dust has been estimated to affect 3.6 million workers within the European Union (EU). The most serious health effect caused by wood dust is the nasal and sinonasal cancer (SNC), which has been observed predominantly among woodworkers. Free radicals produced by inflammatory reactions as a consequence of wood dust could play a major role in SNC development. Therefore, we investigated the association between wood dust and oxidative DNA damage in the cells of nasal epithelia, the target site of SNC. We have analyzed oxidative DNA damage by determining the levels of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (MdG), a major-peroxidation-derived DNA adduct and a biomarker of cancer risk in 136 woodworkers compared to 87 controls in Tuscany, Italy. We then examined the association of MdG with co-exposure to volatile organic compounds (VOCs), exposure length, and urinary 15-F isoprostane (15-F-IsoP), a biomarker of oxidant status. Wood dust at the workplace was estimated by the Information System for Recording Occupational Exposures to Carcinogens. MdG was measured using P-postlabeling and mass spectrometry. 15-F-IsoP was analyzed using ELISA. Results show a significant excess of MdG in the woodworkers exposed to average levels of 1.48 mg/m relative to the controls. The overall mean ratio (MR) between the woodworkers and the controls was 1.28 (95% C.I. 1.03-1.58). After stratification for smoking habits and occupational status (exposure to wood dust alone and co-exposure to VOCs), the association of MdG with wood dust (alone) was even greater in non-smokers workers, MR of 1.43 (95% C.I. 1.09-1.87). Conversely, not consistent results were found in ex-smokers and current smokers. MdG was significantly associated with co-exposure to VOCs, MR of 1.95 (95% C.I. 1.46-2.61), and occupational history, MR of 2.47 (95% C.I. 1.67-3.62). Next, the frequency of MdG was significantly correlated to the urinary excretion of 15-F-IsoP, regression coefficient (β) = 0.442 ± 0.172 (SE). Consistent with the hypothesis of a genotoxic mechanism, we observed an enhanced frequency of MdG adducts in woodworkers, even at the external levels below the regulatory limit. Our data implement the understanding of SNC and could be useful for the management of the adverse effects caused by this carcinogen.
Topics: Cross-Sectional Studies; DNA Adducts; Deoxyguanosine; Dinoprost; Dust; Humans; Italy; Male; Middle Aged; Occupational Exposure; Pyrimidinones; Reference Standards; Wood
PubMed: 31195682
DOI: 10.3390/ijms20112763 -
Nature Communications Dec 2023Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha...
Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.
Topics: Female; Humans; Carboprost; Dinoprost; Latanoprost; Ligands; Receptors, Prostaglandin; Cryoelectron Microscopy
PubMed: 38065938
DOI: 10.1038/s41467-023-43922-8 -
The American Journal of Clinical... Sep 2013It is uncertain whether saturated fatty acids (SFAs) impair endothelial function and contribute to arterial stiffening. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
It is uncertain whether saturated fatty acids (SFAs) impair endothelial function and contribute to arterial stiffening.
OBJECTIVE
We tested the effects of replacing SFAs with monounsaturated fatty acids (MUFAs) or carbohydrates on endothelial function and arterial stiffness.
DESIGN
With the use of a parallel-designed randomized controlled trial in 121 insulin-resistant men and women, we measured vascular function after 1 mo of consumption of a high-SFA (HS) diet and after 24 wk after random assignment to the HS diet or diets that contained <10% SFAs and were high in either MUFAs or carbohydrates. The primary outcome was a change in flow-mediated dilation (FMD), and secondary outcomes were changes in carotid to femoral pulse wave velocity (PWV) and plasma 8-isoprostane F2α-III concentrations.
RESULTS
For 112 participants with data available for analysis on the specified outcomes, no significant differences were shown. FMD with the HS reference diet was 6.7 ± 2.2%, and changes (95% CIs) after 6 mo of intervention were +0.3 (-0.4, 1.1), -0.2 (-0.8, 0.5), and -0.1 (-0.6, 0.7) with HS, high-MUFA (HM), and high-carbohydrate (HC) diets, respectively. After consumption of the HS reference diet, the geometric mean (±SD) PWV was 7.67 ± 1.62 m/s, and mean percentages of changes (95% CIs) were -1.0 (-6.2, 4.3) with the HS diet, 2.7 (-1.4, 6.9) with the HM diet, and -1.0 (-5.5, 3.4) with the HC diet. With the HS reference diet, the geometric mean (±SD) plasma 8-isoprostane F2α-III concentration was 176 ± 85 pmol/L, and mean percentage of changes (95% CIs) were 1 (-12, 14) with the HS diet, 6 (-5, 16) with the HM diet, and 4 (-7, 16) with the HC diet.
CONCLUSION
The replacement of SFAs with MUFAs or carbohydrates in healthy subjects does not affect vascular function. This trial was registered at Current Controlled Trials (http://www.controlled-trials.com/ISRCTN) as ISRCTN 29111298.
Topics: Adult; Diet; Dietary Carbohydrates; Dietary Fats; Dinoprost; Endothelium, Vascular; Fatty Acids; Fatty Acids, Monounsaturated; Female; Humans; Insulin Resistance; Male; Middle Aged; Pulse; Vascular Diseases; Vascular Stiffness; Vasodilation
PubMed: 23964054
DOI: 10.3945/ajcn.113.063644 -
The British Journal of Ophthalmology Mar 2006This study illustrates the difficulty of sorting out basic mechanisms of action with clinical techniques
This study illustrates the difficulty of sorting out basic mechanisms of action with clinical techniques
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Dinoprost; Drug Interactions; Humans; Ocular Hypertension; Prostaglandins, Synthetic
PubMed: 16488938
DOI: 10.1136/bjo.2005.083345 -
Pharmacological Reports : PR 2009Elevated plasma levels of inflammation and endothelial dysfunction markers have been reported in patients with hypertrophic cardiomyopathy (HCM). The aim of the current...
Elevated plasma levels of inflammation and endothelial dysfunction markers have been reported in patients with hypertrophic cardiomyopathy (HCM). The aim of the current study was to determine whether HCM is associated with enhanced oxidative stress. We enrolled 54 HCM patients with sinus rhythm, including 21 subjects with a left ventricular outflow tract (LVOT) obstruction (gradient >/= 30 mmHg), and 54 age- and sex-matched controls without cardiovascular diseases. Serum levels of 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), a stable marker of oxidative stress, were determined. Serum 8-iso-PGF(2alpha) levels were elevated in HCM patients compared with controls (35.4 +/- 10.2 vs. 29.9 +/- 9.9 pg/ml, p < 0.001). Patients with obstructive HCM displayed higher 8-iso-PGF(2alpha) levels compared with the non-obstructive HCM subgroup (41.6 +/- 12.7 vs. 31.4 +/- 5.4 pg/ml, p < 0.0001). Both anatomic (mitral-septal distance) and hemodynamic (subaortic gradient) indexes of LVOT obstruction, but not other echocardiographic variables, correlated with 8-iso-PGF(2alpha) levels (r = -0.43; p < 0.05 and r = 0.39; p < 0.05, respectively). This study is the first to show that HCM is characterized by enhanced oxidative stress as evidenced by higher 8-iso-PGF(2alpha), which achieves its highest values in the presence of LVOT obstruction in HCM patients.
Topics: Cardiomyopathy, Hypertrophic; Cohort Studies; Dinoprost; Echocardiography; Female; Humans; Male; Middle Aged; Oxidative Stress; Ventricular Outflow Obstruction
PubMed: 19605948
DOI: 10.1016/s1734-1140(09)70091-x -
Arquivos de Gastroenterologia 2018Ostomy is a surgical procedure that creates a stoma that aims to construct a new path for the output of feces or urine. The relationship of oxidative stress (OxS)...
BACKGROUND
Ostomy is a surgical procedure that creates a stoma that aims to construct a new path for the output of feces or urine. The relationship of oxidative stress (OxS) markers in patients with ostomy is still poorly described.
OBJECTIVE
The present study was aimed at investigating the changes in oxidative stress parameters in peripheral blood collected from ostomy patients when compared with a healthy control group.
METHODS
It was evaluated 29 ostomy patients and 30 healthy control patients. The oxidative stress parameters evaluated were: lipid peroxidation [lipid hydroperoxide (LPO), 8-isoprostane (8-ISO) and 4-hydroxynonenal (4-HNE)], protein oxidation and nitration [carbonyl and 3-nitrotyrosine (3-NT)] and DNA oxidation [8-hydroxy-2'-deoxyguanosine (8-OHDG)] in serum from ostomy patients compared to health controls.
RESULTS
The data showed an increase of LPO, 8-ISO, 4-HNE, 3-NT and 8-OHDG in serum collected from ostomy patients when compared to healthy controls.
CONCLUSION
The findings support the hypothesis that ostomy triggers the oxidative stress observed in the blood collected from these patients.
Topics: Adult; Aged; Aldehydes; Biomarkers; Case-Control Studies; DNA Damage; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lipid Peroxidation; Lipid Peroxides; Male; Middle Aged; Ostomy; Oxidative Stress; Surgical Stomas; Tyrosine
PubMed: 30043867
DOI: 10.1590/S0004-2803.201800000-29 -
Journal of Dairy Science Nov 2012The objective was to determine the effect of 2 presynchronization treatments on first-service pregnancy per artificial insemination (P/AI) in 4 dairy herds during warm...
Pregnancy per artificial insemination after presynchronizing estrous cycles with the Presynch-10 protocol or prostaglandin F2α injection followed by gonadotropin-releasing hormone before Ovsynch-56 in 4 dairy herds of lactating dairy cows.
The objective was to determine the effect of 2 presynchronization treatments on first-service pregnancy per artificial insemination (P/AI) in 4 dairy herds during warm and cool seasons of the year. Cows with ear tags ending with even digits at calving were enrolled in Presynch-10 (Presynch-10): two 25-mg injections of PGF2α (i.e., PG-1 and PG-2) 14 d apart. Cows with ear tags ending with odd digits were enrolled in PG-3-G: one 25-mg injection of PG (Pre-PG) 3 d before injection of 100μg of GnRH (Pre-GnRH), with the Pre-PG injection administered at the same time as PG-2 in the Presynch-10 treatment. Ten days after PG-2 or Pre-PG, all cows were enrolled in a timed AI protocol (Ovsynch-56; injection of GnRH 7 d before GnRH-1 and 56 h after GnRH-2 PG with AI 16 to 18 h after GnRH-2). Median days in milk (DIM) at scheduled timed AI were 75 d, which did not differ among herds. Cows detected in estrus before the scheduled timed AI were inseminated early (early bred, EB). Pregnancy was diagnosed at d 32 to 38 and at d 60 to 66 after timed AI by transrectal ultrasonography or transrectal palpation. Data were analyzed with herd as a random effect and with fixed effects of treatment (EB, Presynch-10, or PG-3-G), parity (primiparous vs. multiparous), season [hot (June through September) vs. cool-cold (October through May)], DIM, estrus at timed AI (0 vs. 1), and all 2-way interactions with treatment. The P/AI at d 32 to 38 for EB (n=472), Presynch-10 (n=1,247), and PG-3-G (n=1,286) were 31.4, 35.0, and 41.2%, respectively; P/AI at d 60 to 66 was 29.8, 32.2, and 37.3%, respectively. Season significantly influenced P/AI at d 32 to 38 and d 60 to 66, but a treatment by season interaction was not detected. The P/AI for PG-3-G and Presynch-10 treatments did not differ during cool-cold weather (d 32 to 38: 46.8 vs. 44.3%; d 60 to 66: 41.6 vs. 41.1%, respectively), but PG-3-G and Presynch-10 produced more P/AI than EB at d 32 to 38. During the summer, P/AI in PG-3-G was greater than in Presynch-10 (d 32 to 38: 35.9 vs. 26.7% and d 60 to 66: 33.2 vs. 24.4%, respectively), and P/AI in EB cows did not differ from that of Presynch-10 cows. Although pregnancy loss did not differ for EB, Presynch-10, and PG-3-G treatments (4.0, 6.7, and 9.3%, respectively), pregnancy loss from d 32 to 38 and d 60 to 66 was 2-fold greater in thinner cows (<2.5 vs. ≥2.5; 9.0 vs. 4.4%). We concluded that presynchronizing estrous cycles with PG-3-G produced more P/AI than inseminating cows at estrus during cooler weather and was superior to Presynch-10 during the summer.
Topics: Animals; Cattle; Dairying; Dinoprost; Estrus; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Injections; Insemination, Artificial; Lactation; Pregnancy; Seasons
PubMed: 22939782
DOI: 10.3168/jds.2012-5707