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Acta Biochimica Polonica 2014This review compiles the current knowledge on the effects of prostanoids - arachidonic acid metabolites - on their own synthesis, activity and degradation. Interaction... (Review)
Review
This review compiles the current knowledge on the effects of prostanoids - arachidonic acid metabolites - on their own synthesis, activity and degradation. Interaction mechanisms between the receptors for the relevant compounds are presented, in particular with regard to the cooperation between a thromboxane A₂ and prostaglandin I₂ receptors. The questions of desensitization and internalization of receptors are discussed. The stages of the inflammatory response and tumor progression are analyzed against the background of the disruption of the synthesis of prostanoids. Special attention is given to the significance of 15-deoxy-Δ(12,14)-prostaglandin J₂ in the regulation of the synthesis of prostanoids and its role as an anti-inflammatory agent. Ultimately, therapeutic approaches as used in various treatments are discussed in the light of the available knowledge.
Topics: Animals; Humans; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Receptors, Epoprostenol; Receptors, Thromboxane A2, Prostaglandin H2
PubMed: 25343148
DOI: No ID Found -
Indian Journal of Ophthalmology May 2023Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head... (Review)
Review
Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional β-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.
Topics: Humans; Bimatoprost; Cloprostenol; Travoprost; Latanoprost; Prostaglandins F, Synthetic; Ophthalmology; Antihypertensive Agents; Amides; Prostaglandins, Synthetic; Glaucoma; Intraocular Pressure
PubMed: 37203029
DOI: 10.4103/IJO.IJO_2706_22 -
Biological & Pharmaceutical Bulletin 2022Prostaglandins (PGs) are lipid-derived autacoids that are synthesized from arachidonic acid by the action of cyclooxygenases and PG terminal synthases. PGs consist of... (Review)
Review
Prostaglandins (PGs) are lipid-derived autacoids that are synthesized from arachidonic acid by the action of cyclooxygenases and PG terminal synthases. PGs consist of PGD, PGE, PGF, prostacyclin (PGI), and thromboxane A, which act through G protein-coupled receptors. PGs sustain homeostatic functions and exert a variety of pathophysiological roles to regulate the development of various diseases such as obesity and dyslipidemia. Adipocytes (fat cells) have the unique capacity to accumulate large amounts of lipids as energy source in lipid droplets. Adipogenesis is the process of differentiation from preadipocytes to mature adipocytes, which is regulated by various adipogenic transcription factors. Obesity is defined as an abnormal increase in adipose tissue mass and is considered to be a risk factor for the development of lifestyle-related diseases including cardiovascular disease, hyperlipidemia, and type 2 diabetes mellitus. This review summarizes insights into the roles of PGD, PGF, and their synthases in the regulation of adipogenesis and obesity.
Topics: Adipogenesis; Diabetes Mellitus, Type 2; Humans; Obesity; Prostaglandin D2; Prostaglandins; Prostaglandins F
PubMed: 35908908
DOI: 10.1248/bpb.b22-00210 -
Respiratory Research Nov 2023Pulmonary arterial hypertension (PAH), Group 1 pulmonary hypertension (PH), is a type of pulmonary vascular disease characterized by abnormal contraction and remodeling... (Review)
Review
BACKGROUND
Pulmonary arterial hypertension (PAH), Group 1 pulmonary hypertension (PH), is a type of pulmonary vascular disease characterized by abnormal contraction and remodeling of the pulmonary arterioles, manifested by pulmonary vascular resistance (PVR) and increased pulmonary arterial pressure, eventually leading to right heart failure or even death. The mechanisms involved in this process include inflammation, vascular matrix remodeling, endothelial cell apoptosis and proliferation, vasoconstriction, vascular smooth muscle cell proliferation and hypertrophy. In this study, we review the mechanisms of action of prostaglandins and their receptors in PAH.
MAIN BODY
PAH-targeted therapies, such as endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, activators of soluble guanylate cyclase, prostacyclin, and prostacyclin analogs, improve PVR, mean pulmonary arterial pressure, and the six-minute walk distance, cardiac output and exercise capacity and are licensed for patients with PAH; however, they have not been shown to reduce mortality. Current treatments for PAH primarily focus on inhibiting excessive pulmonary vasoconstriction, however, vascular remodeling is recalcitrant to currently available therapies. Lung transplantation remains the definitive treatment for patients with PAH. Therefore, it is imperative to identify novel targets for improving pulmonary vascular remodeling in PAH. Studies have confirmed that prostaglandins and their receptors play important roles in the occurrence and development of PAH through vasoconstriction, vascular smooth muscle cell proliferation and migration, inflammation, and extracellular matrix remodeling.
CONCLUSION
Prostacyclin and related drugs have been used in the clinical treatment of PAH. Other prostaglandins also have the potential to treat PAH. This review provides ideas for the treatment of PAH and the discovery of new drug targets.
Topics: Humans; Prostaglandins; Pulmonary Arterial Hypertension; Receptors, Prostaglandin; Vascular Remodeling; Familial Primary Pulmonary Hypertension; Epoprostenol; Prostaglandins I; Inflammation; Pulmonary Artery
PubMed: 37915044
DOI: 10.1186/s12931-023-02559-3 -
Biomolecules May 2021Organ fibrosis is a common pathological result of various chronic diseases with multiple causes. Fibrosis is characterized by the excessive deposition of extracellular... (Review)
Review
Organ fibrosis is a common pathological result of various chronic diseases with multiple causes. Fibrosis is characterized by the excessive deposition of extracellular matrix and eventually leads to the destruction of the tissue structure and impaired organ function. Prostaglandins are produced by arachidonic acid through cyclooxygenases and various prostaglandin-specific synthases. Prostaglandins bind to homologous receptors on adjacent tissue cells in an autocrine or paracrine manner and participate in the regulation of a series of physiological or pathological processes, including fibrosis. This review summarizes the properties, synthesis, and degradation of various prostaglandins, as well as the roles of these prostaglandins and their receptors in fibrosis in multiple models to reveal the clinical significance of prostaglandins and their receptors in the treatment of fibrosis.
Topics: Animals; Autocrine Communication; Chronic Disease; Fibrosis; Humans; Paracrine Communication; Prostaglandin-Endoperoxide Synthases; Prostaglandins
PubMed: 34073892
DOI: 10.3390/biom11060789 -
British Journal of Pharmacology Apr 2019This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit...
This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.
Topics: Animals; History, 20th Century; Humans; Nobel Prize; Physiology; Prostaglandin-Endoperoxide Synthases; Prostaglandins
PubMed: 30953367
DOI: 10.1111/bph.14588 -
International Journal of Molecular... Feb 2021In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are... (Review)
Review
In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF and 1,15-PGF lactones, many 1,15-lactones of E, E, F, F, A, and A were found in the marine mollusc and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.
Topics: Catalysis; Lactones; Molecular Structure; Prostaglandins; Prostaglandins, Synthetic
PubMed: 33557221
DOI: 10.3390/ijms22041572 -
Journal of Optometry 2024To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF)...
Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells.
PURPOSE
To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC.
METHODS
Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC.
RESULTS
BAK-preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK-preserved bimatoprost by 45% (p = 0.006), PQ-preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not.
CONCLUSION
BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops.
Topics: Humans; Benzalkonium Compounds; Travoprost; Latanoprost; Ophthalmic Solutions; Goblet Cells; Bimatoprost; Cloprostenol; Interleukin-8; Prostaglandins F, Synthetic; Antihypertensive Agents; Preservatives, Pharmaceutical; Prostaglandins, Synthetic
PubMed: 37788596
DOI: 10.1016/j.optom.2023.100481 -
Korean Journal of Ophthalmology : KJO Jun 2021To evaluate the safety and efficacy of preservative-free (PF) latanoprost in glaucoma patients. (Observational Study)
Observational Study
PURPOSE
To evaluate the safety and efficacy of preservative-free (PF) latanoprost in glaucoma patients.
METHODS
In this prospective, open-label, observational study, a total of 27 primary open-angle glaucoma patients who used benzalkonium chloride-preserved prostaglandin analogues for at least 6 months were enrolled. After changing the eye drops to PF lataprost, the intraocular pressure (IOP) and ocular surface symptoms and signs were evaluated in all patients on days 0 (first visit, D0), 45 (D45), and 90 (D90).
RESULTS
Mean IOP remained stable during the study period (14.0 ± 2.4 mmHg at D0, 13.9 ± 2.0 mmHg at D45, 13.7 ± 2.2 mmHg at D90; p = 0.603). Mean deviation, pattern standard deviation, and best-corrected visual acuity were similar before and after eye drops replacement. Bulbar conjunctival hyperemia, corneal staining, and conjunctival staining were significantly decreased over 90 days (p = 0.025, p < 0.001, p = 0.020, respectively). The ocular surface disease index score showed a statistically significant improvement from 26.4 ± 18.5 at D0 to 19.8 ± 17.0 at D45 and 15.7 ± 15.6 at D90 (p < 0.001). In the evaluation of ocular tolerability, burning symptoms and dryness were significantly decreased (p = 0.001, p = 0.040).
CONCLUSIONS
The effects of PF latanoprost on reducing IOP were comparable with those of benzalkonium chloride-preserved prostaglandin analogues, but side effects on the ocular surface were much less pronounced when PF latanoprost was used. With this efficacy, PF latanoprost could slow the progression of glaucoma by increasing patient compliance.
Topics: Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prospective Studies; Prostaglandins F, Synthetic; Prostaglandins, Synthetic
PubMed: 34120423
DOI: 10.3341/kjo.2021.0010 -
Proceedings of the Japan Academy.... 2017Non-steroidal anti-inflammatory drugs (NSAIDs) exert their anti-inflammatory and anti-tumor effects by reducing prostaglandin (PG) production via the inhibition of... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) exert their anti-inflammatory and anti-tumor effects by reducing prostaglandin (PG) production via the inhibition of cyclooxygenase (COX). However, the gastrointestinal, renal and cardiovascular side effects associated with the pharmacological inhibition of the COX enzymes have focused renewed attention onto other potential targets for NSAIDs. PGH, a COX metabolite, is converted to each PG species by species-specific PG terminal synthases. Because of their potential for more selective modulation of PG production, PG terminal synthases are now being investigated as a novel target for NSAIDs. In this review, I summarize the current understanding of PG terminal synthases, with a focus on microsomal PGE synthase-1 (mPGES-1) and PGI synthase (PGIS). mPGES-1 and PGIS cooperatively exacerbate inflammatory reactions but have opposing effects on carcinogenesis. mPGES-1 and PGIS are expected to be attractive alternatives to COX as therapeutic targets for several diseases, including inflammatory diseases and cancer.
Topics: Amino Acid Sequence; Animals; Disease; Drug Discovery; Humans; Ligases; Molecular Targeted Therapy; Prostaglandins
PubMed: 29129850
DOI: 10.2183/pjab.93.044