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Journal of Pain & Palliative Care... Jun 2017Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which... (Review)
Review
Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Osteoarthritis
PubMed: 28388238
DOI: 10.1080/15360288.2017.1301616 -
Advanced Science (Weinheim,... Feb 2023CD73, a cell surface-bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5'-AMP to adenosine. Several studies have shown that CD73 plays an...
CD73, a cell surface-bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5'-AMP to adenosine. Several studies have shown that CD73 plays an essential role in immune escape, cell proliferation and tumor angiogenesis, making it an attractive target for cancer therapies. However, there are limited clinical benefits associated with the mainstream enzymatic inhibitors of CD73, suggesting that the mechanism underlying the role of CD73 in tumor progression is more complex than anticipated, and further investigation is necessary. In this study, CD73 is found to overexpress in the cytoplasm of pancreatic ductal adenocarcinoma (PDAC) cells and promotes metastasis in a nucleotidase-independent manner, which cannot be restrained by the CD73 monoclonal antibodies or small-molecule enzymatic inhibitors. Furthermore, CD73 promotes the metastasis of PDAC by binding to the E3 ligase TRIM21, competing with the Snail for its binding site. Additionally, a CD73 transcriptional inhibitor, diclofenac, a non-steroidal anti-inflammatory drug, is more effective than the CD73 blocking antibody for the treatment of PDAC metastasis. Diclofenac also enhances the therapeutic efficacy of gemcitabine in the spontaneous KPC (LSL-Kras , LSL-Trp53 , and Pdx-1-Cre) pancreatic cancer model. Therefore, diclofenac may be an effective anti-CD73 therapy, when used alone or in combination with gemcitabine-based chemotherapy regimen, for metastatic PDAC.
Topics: Humans; Carcinoma, Pancreatic Ductal; Diclofenac; Gemcitabine; Pancreatic Neoplasms; Nucleotidases
PubMed: 36563135
DOI: 10.1002/advs.202206335 -
ACS Nano Dec 2023Meniscus injuries are associated with the degeneration of cartilage and development of osteoarthritis (OA). It is challenging to protect articular cartilage and improve...
Meniscus injuries are associated with the degeneration of cartilage and development of osteoarthritis (OA). It is challenging to protect articular cartilage and improve exercise when a meniscus injury occurs. Herein, inspired by the components and functions of the meniscus, we developed a self-lubricating and friction-responsive hydrogel that contains nanoliposomes loaded with diclofenac sodium (DS) and Kartogenin (KGN) for anti-inflammation and cartilage regeneration. When the hydrogel was injected into the meniscus injury site, the drug-loaded nanoliposomes were released from the hydrogel in a friction-responsive manner and reassembled to form hydration layers that lubricate joints during movement. Meanwhile, DS and KNG were constantly released from the nanoliposomes to mitigate inflammation and promote cartilage regeneration. Additionally, this hydrogel exhibited favorable injectability, mechanical properties, fatigue resistance, and prolonged degradation. experiments demonstrated that injection of the hydrogel effectively improved exercise performance and protected the articular cartilage of rats, suggesting it as a potential therapeutic approach for meniscal injuries.
Topics: Rats; Animals; Cartilage, Articular; Hydrogels; Friction; Meniscus; Injections; Diclofenac
PubMed: 37975685
DOI: 10.1021/acsnano.3c10139 -
International Immunopharmacology Aug 2018The anti-inflammatory and immunomodulatory effects of nanoparticles in several chronic diseases have been extensively researched. The aim of this review is to examine... (Review)
Review
The anti-inflammatory and immunomodulatory effects of nanoparticles in several chronic diseases have been extensively researched. The aim of this review is to examine how nanoparticles modulate the inflammatory pathways that characterize the most prevalent forms of microcrystal-induced arthritis, including gout, pseudogout, and BCP-induced arthritis. The nanoparticles of chitosan-coated calcium phosphate, uricase, aceclofenac, and gold have been investigated in crystal-inducedarthritis. The most important results of the studies outlined in this review show that nanoparticles can inhibit the expression and the release of some pro-inflammatory mediators and proteolytic enzymes, and the activity of different transcriptional factors in vitro, as well as decrease the uric acid levels in several studies of in vitro and in vivo models of gout, which show interesting results in terms of decreasing the amount of crystals and tissue damage, respectively. In view of their multiple beneficial effects, nanoparticles can be considered a valuable therapy that contributes to the pharmacological treatment in crystalinduced arthritis.
Topics: Animals; Calcium Phosphates; Chitosan; Chondrocalcinosis; Crystal Arthropathies; Diclofenac; Disease Models, Animal; Gold; Humans; Inflammation Mediators; Nanoparticles; Peptide Hydrolases; Urate Oxidase; Uric Acid
PubMed: 29890413
DOI: 10.1016/j.intimp.2018.06.007 -
Andrologia Jun 2021Diclofenac is an effective nonsteroidal anti-inflammatory drug and one of the most prescribed medicines worldwide. So far, there are many published articles that... (Review)
Review
Diclofenac is an effective nonsteroidal anti-inflammatory drug and one of the most prescribed medicines worldwide. So far, there are many published articles that directly link between diclofenac and semen quality; however, hitherto, there is no collective review or comprehensive discussion that reveal such imperative link. Therefore, this work reviews and judges the association between diclofenac administration and semen quality, henceforth male infertility. As a tool to accomplish this scientific input, Scopus, Embase and PubMed databases have been searched for all original articles using the keywords "diclofenac" versus "semen" and "sperm" since August 1987 through November 2020. In summary, diclofenac appears to induce negative effects on both qualitative and quantitative measures of sperm; however, this conclusion requires confirmation by human studies. The detected negative effects of diclofenac on semen quality measures may be owed to reduced levels of gonadal hormones, decreased antioxidant defence mechanism, increased oxidative stress, altered concentrations of nitric oxide that are required to maintain normal sperm physiology and reduced synthesis of prostaglandins.
Topics: Diclofenac; Humans; Infertility, Male; Male; Semen; Semen Analysis; Spermatozoa
PubMed: 33650710
DOI: 10.1111/and.14021 -
Marine Pollution Bulletin Jun 2018Interest in the presence and effects of diclofenac (DCF) and other pharmaceutical products (PPs) in the aquatic environment has been growing over the last 20 years.... (Review)
Review
Interest in the presence and effects of diclofenac (DCF) and other pharmaceutical products (PPs) in the aquatic environment has been growing over the last 20 years. DCF has been included in the First Watch List of the EU Water Framework Directive in order to gather monitoring data in surface waters. Despite PP input in water bodies, few studies have been conducted to determine the extent of DCF occurrence and effects on marine ecosystems, which is usually the final recipient of surface waters. The present article reviews available published data on DCF occurrence in marine water, sediment and organisms, and its effects on marine organisms. The findings highlight the scarcity of available data on the occurrence and effects of DCF in marine ecosystems, and the need for further data acquisition to assess the risks associated with the presence of this compound in the environment.
Topics: Aquatic Organisms; Diclofenac; Ecosystem; Geologic Sediments; Water Pollutants, Chemical
PubMed: 29886975
DOI: 10.1016/j.marpolbul.2018.04.053 -
The Science of the Total Environment Nov 2021Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in livestock farming, with lethal effects on vultures when reaching high concentrations in the... (Review)
Review
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used in livestock farming, with lethal effects on vultures when reaching high concentrations in the carcasses they feed on. There are evidences showing that it caused the decline of >95% of vultures of the Gyps genus in Southern Asia until its ban in 2006. In March 2013 two veterinary drugs containing diclofenac were authorized in Spain. The scientific and conservationist communities alerted on the foreseeable risks to European vulture populations based on previous experiences. Several risk assessments modelled the expected impact on vultures, and media campaigns were launched to ban the veterinary use of diclofenac. Here, we evaluate the situation of Spanish vultures after seven years (2013-2019) since the marketing authorisation of the veterinary use of diclofenac was granted. The present assessment takes into consideration the awareness measures adopted to avoid an inappropriate use of the drug, the results of the monitoring programs performed both for vultures and livestock in the wild and from toxicological tests, as well as the review of the published models on the expected mortality of vultures. The measures adopted seem to have been adequate and have avoided impacts at vulture population level despite the finding of one cinereous vulture lethally intoxicated by diclofenac in 2020. In view of the results, we discuss the different situations from the veterinary use of this drug between Southern Asia and Spain. Finally, surveillance priorities and future prospects are proposed to prevent risks from possible changes in the current circumstances, regarding the use of diclofenac and other NSAIDs potentially harmful like flunixin.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Falconiformes; Spain; Veterinary Drugs
PubMed: 34271379
DOI: 10.1016/j.scitotenv.2021.148851 -
Ecotoxicology and Environmental Safety Nov 2022Diclofenac is an emerging surface water contaminant, yet the environmental impact of its degradation products remains elusive. The current study focuses on...
Diclofenac is an emerging surface water contaminant, yet the environmental impact of its degradation products remains elusive. The current study focuses on mineralogy-controlled diclofenac photo-degradation and its potential health impacts. Under irradiated conditions, we studied the effects of kaolinite, hematite, and anatase on diclofenac degradation. Our results showed that kaolinite doubled the diclofenac degradation rate, which can be attributed to the high catalytic effect, mediated via increased surface area and pore size of mineral surface in the low pH. Conversely, anatase, a crystal phase of titanium dioxide (TiO), diminished the diclofenac degradation compared to treatments without TiO. Hematite, on the other hand, showed no effect on diclofenac degradation. Photo-degradation products also varied with the mineral surface. We further assessed in vitro toxicological effects of photo-degraded products on two human cell lines, HEK293T and HepG2. Biological assays confirmed that photo-degraded compound 6 (1-(2,6-dichlorophenyl)indolin-2-one) decreased HEK293T cell survival significantly (p < 0.05) when compared to diclofenac in all concentrations. At lower concentrations, inhibition of HEK293T cells caused by compounds 4 (2-(8-chloro-9H-carbazol-1-yl)acetic acid), and 5 (2-(9H-carbazol-1-yl)acetic acid) was greater than diclofenac. Compound 7 (1-phenylindolin-2-one) was toxic only at 250 µM. Additionally, compound 6 decreased HepG2 cell viability significantly when compared to diclofenac. Overall, our data highlighted that mineralogy plays a vital role in environmental diclofenac transformation and its photo-degraded products. Some photo-degraded compounds can be more cytotoxic than the parent compound, diclofenac.
Topics: Humans; Diclofenac; Kaolin; HEK293 Cells; Titanium; Water Pollutants, Chemical
PubMed: 36201921
DOI: 10.1016/j.ecoenv.2022.114138 -
Environmental Science & Technology Aug 2022Diclofenac (DCF) is a pharmaceutically active contaminant frequently found in aquatic ecosystems. The transformation pathways and microbiology involved in the...
Diclofenac (DCF) is a pharmaceutically active contaminant frequently found in aquatic ecosystems. The transformation pathways and microbiology involved in the biodegradation of DCF, particularly under anoxic conditions, remain poorly understood. Here, we demonstrated microbially mediated reductive dechlorination of DCF in anaerobic enrichment culture derived from contaminated river sediment. Over 90% of the initial 76.7 ± 3.6 μM DCF was dechlorinated at a maximum rate of 1.8 ± 0.3 μM day during a 160 days' incubation. Mass spectrometric analysis confirmed that 2-(2-((2-chlorophenyl)amino)phenyl)acetic acid (2-CPA) and 2-anilinophenylacetic acid (2-APA) were formed as the monochlorinated and nonchlorinated DCF transformation products, respectively. A survey of microbial composition and Sanger sequencing revealed the enrichment and dominance of a new population, designated as sp. strain DCF, in the DCF-dechlorinating community. Following the stoichiometric conversion of DCF to 2-CPA (76.0 ± 2.1 μM) and 2-APA (3.7 ± 0.8 μM), strain DCF cell densities increased by 24.4 ± 4.4-fold with a growth yield of 9.0 ± 0.1 × 10 cells per μmol chloride released. Our findings expand the metabolic capability in the genus and highlight the relevant roles of organohalide-respiring bacteria for the natural attenuation of halogenated contaminants of emerging concerns (e.g., DCF).
Topics: Biodegradation, Environmental; Chloroflexi; Diclofenac; Ecosystem; Respiration
PubMed: 35921385
DOI: 10.1021/acs.est.1c08824 -
Environment International Nov 2016Diclofenac (DCF) is a prevalent anti-inflammatory drug used throughout the world. Intensive researches carried out in the past few decades have confirmed the global... (Review)
Review
Diclofenac (DCF) is a prevalent anti-inflammatory drug used throughout the world. Intensive researches carried out in the past few decades have confirmed the global ubiquity of DCF in various environmental compartments. Its frequent occurrence in freshwater environments and its potential toxicity towards several organisms such as fish and mussels makes DCF an emerging environmental contaminant. At typical detected environmental concentrations, the drug does not exhibit toxic effects towards living organisms, albeit chronic exposure may lead to severe effects. For DCF, about 30-70% removal has been obtained through the conventional treatment system in wastewater treatment plant being the major primary sink. Thus, the untreated DCF will pass to surface water. DCF can interact with other inorganic contaminants in the environment particularly in wastewater treatment plant, such as metals, organic contaminants and even with DCF metabolites. This process may lead to the creation of another possible emerging contaminant. In the present context, environmental fate of DCF in different compartments such as soil and water has been addressed with an overview of current treatment methods. In addition, the toxicity concerns regarding DCF in aquatic as well as terrestrial environment along with an introduction to the metabolites of DCF through consumption as well as abiotic degradation routes are also discussed. Further studies are required to better assess the fate and toxicological effects of DCF and its metabolites and must consider the possible interaction of DCF with other contaminants to develop an effective treatment method for DCF and its traces.
Topics: Animals; Diclofenac; Environment; Environmental Pollution; Humans; Wastewater; Water Pollutants, Chemical
PubMed: 27649472
DOI: 10.1016/j.envint.2016.09.014