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Tissue & Cell Oct 2023Diclofenac, a non-steroidal anti-inflammatory drug, reportedly targets mitochondria and induces nephrotoxicity via reactive oxygen species. However, there are few...
Diclofenac, a non-steroidal anti-inflammatory drug, reportedly targets mitochondria and induces nephrotoxicity via reactive oxygen species. However, there are few detailed reports of pathological analyses of mitochondria and the factors that cause acute kidney injury (AKI) as a result of nephrotoxicity. In this study, we investigated mitochondrial damage in the proximal tubule in AKI mice at 6, 12, and 24 h after administration of diclofenac. Statistical analysis of immunohistochemistry results confirmed that expression of p62 and LC3, which is associated with autophagy, reached a maximum level in the degenerated proximal renal tubule 12 h after diclofenac treatment, with high autophagy activity. Electron microscopy images provided clear evidence that confirmed mitochondrial degeneration and injury as well as autophagy (mitophagy) in mitochondria treated with diclofenac. The purpose of this study was to pathologically characterize both mitochondrial damage in the proximal renal tubules induced by diclofenac and the course of mitophagy to remove the damaged mitochondria. This report provides important information regarding mitochondrial damage in the proximal tubules in diclofenac-induced nephropathy.
Topics: Mice; Animals; Kidney Tubules, Proximal; Diclofenac; Acute Kidney Injury; Mitochondria; Autophagy
PubMed: 37567074
DOI: 10.1016/j.tice.2023.102188 -
Marine Drugs Jul 2023Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for...
Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for biomedical applications. Herein, chitosan (CHT), a natural polymer, and virgin coconut oil (VCO), a resource obtained from coconut kernels, were combined to create an emulsion system. Phytantriol-based cubosomes encapsulating sodium diclofenac, an anti-inflammatory drug, were further dispersed into CHT/VCO- based emulsion. Then, the emulsions were frozen and freeze-dried to produce scaffolds. The scaffolds had a porous structure ranging from 20.4 to 73.4 µm, a high swelling ability (up to 900%) in PBS, and adequate stiffness, notably in the presence of cubosomes. Moreover, a well-sustained release of the entrapped diclofenac in the cubosomes into the CHT/VCO-based system, with an accumulated release of 45 ± 2%, was confirmed in PBS, compared to free diclofenac dispersed (80 ± 4%) into CHT/VCO-based structures. Overall, the present approach opens up new avenues for designing porous biomaterials for drug delivery through a sustainable pathway.
Topics: Chitosan; Emulsions; Diclofenac; Plant Oils; Coconut Oil
PubMed: 37504925
DOI: 10.3390/md21070394 -
The Science of the Total Environment Dec 2023Urbanisation, population growth, and climate change have put unprecedented pressure on water resources, leading to a global water crisis and the need for water reuse....
Urbanisation, population growth, and climate change have put unprecedented pressure on water resources, leading to a global water crisis and the need for water reuse. However, water reuse is unsafe unless persistent chemical pollutants are removed from reclaimed water. State-of-the-art technologies for the reduction of persistent chemical pollutants in wastewater typically impose high operational and energy costs and potentially generate toxic by-products (e.g., bromate from ozonation). Nature-base solutions are preferred to these technologies for their lower environmental impact. However, so far, bio-based tertiary wastewater treatments have been inefficient for industrial-scale applications. Moreover, they often demand significant financial investment and large infrastructure, undermining sustainability objectives. Here, we present a scalable, low-cost, low-carbon, and retrofittable nature-inspired solution to remove persistent chemical pollutants (pharmaceutical, pesticides and industrial chemicals). We showed Daphnia's removal efficiency of individual chemicals and chemicals from wastewater at laboratory scale ranging between 50 % for PFOS and 90 % for diclofenac. We validated the removal efficiency of diclofenac at prototype scale, showing sustained performance over four weeks in outdoor seminatural conditions. A techno-commercial analysis on the Daphnia-based technology suggested several technical, commercial and sustainability advantages over established and emerging treatments at comparable removal efficiency, benchmarked on available data on individual chemicals. Further testing of the technology is underway in open flow environments holding real wastewater. The technology has the potential to improve the quality of wastewater effluent, meeting requirements to produce water appropriate for reuse in irrigation, industrial application, and household use. By preventing persistent chemicals from entering waterways, this technology has the potential to maximise the shift to clean growth, enabling water reuse, reducing resource depletion and preventing environmental pollution.
Topics: Animals; Wastewater; Waste Disposal, Fluid; Cladocera; Diclofenac; Water Purification; Environmental Pollutants; Water Pollutants, Chemical
PubMed: 37739075
DOI: 10.1016/j.scitotenv.2023.167224 -
Environmental Pollution (Barking, Essex... Dec 2022Although the presence of pharmaceuticals in the environment is an issue widely addressed in research over the past two decades, still little is known about their...
Although the presence of pharmaceuticals in the environment is an issue widely addressed in research over the past two decades, still little is known about their transformation products. However, there are indications that some of these chemicals may be equally or even more harmful than parent compounds. Diclofenac (DCF) is among the most commonly detected pharmaceuticals in the aquatic environment, but the potential effects of its metabolites on organisms are poorly understood. Therefore, the present study aimed to evaluate and compare the toxicity of DCF and its metabolite, 4-hydroxy diclofenac (4-OH DCF), in mussels using a multi-biomarker approach. Mytilus trossulus mussels were exposed to DCF and 4-OH DCF at 68.22 and 20.85 μg/L (measured concentrations at day 0), respectively, for 7 days. In our work, we showed that both tested compounds have no effect on most of the enzymatic biomarkers tested. However, it has been shown that their action can affect the protein content in gills and also be reflected through histological markers. ENVIRONMENTAL IMPLICATION: Studies in recent years clearly prove that pharmaceuticals can negatively affect aquatic organisms. In addition to parent compounds, metabolites of pharmaceuticals can also be a significant environmental problem. In the present work, the effects of diclofenac and its main metabolite, 4-hydroxy diclofenac, on marine mussels were evaluated. Both compounds showed negative effects on mussels, which was primarily observed through histological changes. The present study therefore confirms that not only diclofenac, but also its main metabolite can have negative effects on aquatic organisms.
Topics: Animals; Mytilus; Diclofenac; Water Pollutants, Chemical; Aquatic Organisms; Biomarkers; Pharmaceutical Preparations
PubMed: 36223851
DOI: 10.1016/j.envpol.2022.120384 -
Drug Design, Development and Therapy 2022Studies regarding treatment of acute toxicity with diclofenac (ATD) are quite few. Diclofenac is commonly prescribed in neurology, psychiatry, and general medicine...
BACKGROUND
Studies regarding treatment of acute toxicity with diclofenac (ATD) are quite few. Diclofenac is commonly prescribed in neurology, psychiatry, and general medicine practice. This study investigated possible colon-protective effects exerted by Ajwa date fruit extract (ADFE), a prophetic medicine remedy native to Al-Madinah, Saudi Arabia against ATD. Phytochemicals in ADFE as gallic acid and quercetin have reported protective effects against ATD.
METHODS
Total phenols and flavonoids in ADFE were estimated as equivalents to gallic acid and quercetin. Four experimental groups were allocated each of six rats: control group, ATD group received a single dose of 150 mg diclofenac intraperitoneally, toxicity prevention group received a single dose of ADFE orally followed 4 hours later by diclofenac injection, and toxicity treatment group received a similar diclofenac dose followed 4 hours later by a single dose of ADFE. Four days later, animals were sacrificed. Histological and biochemical examinations were done.
RESULTS
ADFE has a total phenolic content of 331.7 gallic acid equivalent/gram extract and a total flavonoid content of 70.23 quercetin equivalent/gram. ATD significantly increased oxidative stress markers as serum malondialdehyde (MDA) and hydrogen peroxide (HO). Serum MDA and HO were significantly scavenged by ADFE. ATD significantly (p<0.001) decreased antioxidant power as serum total antioxidant capacity and catalase activity. That was reversed by ADFE in both prevention and treatment groups. Histologically, ATD caused complete destruction of colonic crypts architecture, patchy loss of the crypts, loss of the surface epithelium, absent goblet cells and submucosal exudate, heavy infiltration of the lamina propria and submucosa with inflammatory cells, mainly lymphocytes and eosinophils. There were mucosal haemorrhages and submucosal dilated congested blood vessels. All that was prevented and treated using ADFE.
CONCLUSION
ADFE is rich in quercetin and gallic acid equivalents that exert potent antitoxic effects. ADFE is strongly recommended for preventive and therapeutic colon effects against ATD.
Topics: Animals; Antioxidants; Diclofenac; Flavonoids; Gallic Acid; Hydrogen Peroxide; Phenols; Phoeniceae; Plant Extracts; Quercetin; Rats
PubMed: 35965961
DOI: 10.2147/DDDT.S344247 -
Environmental Science & Technology Jun 2021The exposure of ecologically critical invertebrate species to biologically active pharmaceuticals poses a serious risk to the aquatic ecosystem. Yet, the fate and toxic...
The exposure of ecologically critical invertebrate species to biologically active pharmaceuticals poses a serious risk to the aquatic ecosystem. Yet, the fate and toxic effects of pharmaceuticals on these nontarget aquatic invertebrates and the underlying mechanisms are poorly studied. Herein, we investigated the toxicokinetic (TK) processes (i.e., uptake, biotransformation, and elimination) of the pharmaceutical diclofenac and its biotransformation in the freshwater invertebrate . We further employed mass spectrometry-based metabolomics to assess the toxic effects of diclofenac on the metabolic functions of . exposed to environmentally relevant concentrations (10 and 100 μg/L). The TK results showed a quick uptake of diclofenac by . (maximum internal concentration of 1.9 μmol/kg) and rapid formation of the conjugate diclofenac taurine (maximum internal concentration of 80.6 μmol/kg), indicating over 40 times higher accumulation of diclofenac taurine than that of diclofenac in . . Depuration kinetics demonstrated that the elimination of diclofenac taurine was 64 times slower than diclofenac in . . Metabolomics results suggested that diclofenac inhibited prostaglandin synthesis and affected the carnitine shuttle pathway at environmentally relevant concentrations. These findings shed light on the significance of the TK process of diclofenac, especially the formation of diclofenac taurine, as well as the sublethal effects of diclofenac on the bulk metabolome of . . Combining the TK processes and metabolomics provides complementary insights and thus a better mechanistic understanding of the effects of diclofenac in aquatic invertebrates.
Topics: Amphipoda; Animals; Diclofenac; Ecosystem; Invertebrates; Metabolomics; Pharmaceutical Preparations; Toxicokinetics; Water Pollutants, Chemical
PubMed: 34086445
DOI: 10.1021/acs.est.0c07887 -
BMJ Case Reports Jan 2019Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome was first described as chronic recurrent multifocal osteomyelitis. Because of its rarity, a...
Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome was first described as chronic recurrent multifocal osteomyelitis. Because of its rarity, a thorough description of its clinical manifestations is lacking. Herein, we describe the clinical manifestations and imaging features, especially the enthesopathy in bilateral Achilles tendons, of a middle-aged Asian woman with SAPHO syndrome, who improved after diclofenac treatment.
Topics: Achilles Tendon; Acquired Hyperostosis Syndrome; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Diagnosis, Differential; Diclofenac; Enthesopathy; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Osteomyelitis; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Whole Body Imaging
PubMed: 30617190
DOI: 10.1136/bcr-2018-225929 -
The Cochrane Database of Systematic... Apr 2021Trigger finger is a common hand condition that occurs when movement of a finger flexor tendon through the first annular (A1) pulley is impaired by degeneration,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trigger finger is a common hand condition that occurs when movement of a finger flexor tendon through the first annular (A1) pulley is impaired by degeneration, inflammation, and swelling. This causes pain and restricted movement of the affected finger. Non-surgical treatment options include activity modification, oral and topical non-steroidal anti-inflammatory drugs (NSAIDs), splinting, and local injections with anti-inflammatory drugs.
OBJECTIVES
To review the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) versus placebo, glucocorticoids, or different NSAIDs administered by the same route for trigger finger.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, CNKI (China National Knowledge Infrastructure), ProQuest Dissertations and Theses, www.ClinicalTrials.gov, and the WHO trials portal until 30 September 2020. We applied no language or publication status restrictions.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) and quasi-randomised trials of adult participants with trigger finger that compared NSAIDs administered topically, orally, or by injection versus placebo, glucocorticoid, or different NSAIDs administered by the same route.
DATA COLLECTION AND ANALYSIS
Two or more review authors independently screened the reports, extracted data, and assessed risk of bias and GRADE certainty of evidence. The seven major outcomes were resolution of trigger finger symptoms, persistent moderate or severe symptoms, recurrence of symptoms, total active range of finger motion, residual pain, patient satisfaction, and adverse events. Treatment effects were reported as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs).
MAIN RESULTS
Two RCTs conducted in an outpatient hospital setting were included (231 adult participants, mean age 58.6 years, 60% female, 95% to 100% moderate to severe disease). Both studies compared a single injection of a non-selective NSAID (12.5 mg diclofenac or 15.0 mg ketorolac) given at lower than normal doses with a single injection of a glucocorticoid (triamcinolone 20 mg or 5 mg), with maximum follow-up duration of 12 weeks or 24 weeks. In both studies, we detected risk of attrition and performance bias. One study also had risk of selection bias. The effects of treatment were sensitive to assumptions about missing outcomes. All seven outcomes were reported in one study, and five in the other. NSAID injection may offer little to no benefit over glucocorticoid injection, based on low- to very low-certainty evidence from two trials. Evidence was downgraded for bias and imprecision. There may be little to no difference between groups in resolution of symptoms at 12 to 24 weeks (34% with NSAIDs, 41% with glucocorticoids; absolute effect 7% lower, 95% confidence interval (CI) 16% lower to 5% higher; 2 studies, 231 participants; RR 0.83, 95% CI 0.62 to 1.11; low-certainty evidence). The rate of persistent moderate to severe symptoms may be higher at 12 to 24 weeks in the NSAIDs group (28%) compared to the glucocorticoid group (14%) (absolute effect 14% higher, 95% CI 2% to 33% higher; 2 studies, 231 participants; RR 2.03, 95% CI 1.19 to 3.46; low-certainty evidence). We are uncertain whether NSAIDs result in fewer recurrences at 12 to 24 weeks (1%) compared to glucocorticoid (21%) (absolute effect 20% lower, 95% CI 21% to 13% lower; 2 studies, 231 participants; RR 0.07, 95% CI 0.01 to 0.38; very low-certainty evidence). There may be little to no difference between groups in mean total active motion at 24 weeks (235 degrees with NSAIDs, 240 degrees with glucocorticoid) (absolute effect 5% lower, 95% CI 34.54% lower to 24.54% higher; 1 study, 99 participants; MD -5.00, 95% CI -34.54 to 24.54; low-certainty evidence). There may be little to no difference between groups in residual pain at 12 to 24 weeks (20% with NSAIDs, 24% with glucocorticoid) (absolute effect 4% lower, 95% CI 11% lower to 7% higher; 2 studies, 231 participants; RR 0.84, 95% CI 0.54 to 1.31; low-certainty evidence). There may be little to no difference between groups in participant-reported treatment success at 24 weeks (64% with NSAIDs, 68% with glucocorticoid) (absolute effect 4% lower, 95% CI 18% lower to 15% higher; 1 study, 121 participants; RR 0.95, 95% CI 0.74 to 1.23; low-certainty evidence). We are uncertain whether NSAID injection has an effect on adverse events at 12 to 24 weeks (1% with NSAIDs, 1% with glucocorticoid) (absolute effect 0% difference, 95% CI 2% lower to 3% higher; 2 studies, 231 participants; RR 2.00, 95% CI 0.19 to 21.42; very low-certainty evidence).
AUTHORS' CONCLUSIONS
For adults with trigger finger, by 24 weeks' follow-up, results from two trials show that compared to glucocorticoid injection, NSAID injection offered little to no benefit in the treatment of trigger finger. Specifically, there was no difference in resolution, symptoms, recurrence, total active motion, residual pain, participant-reported treatment success, or adverse events.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Bias; Diclofenac; Female; Glucocorticoids; Humans; Ketorolac; Male; Middle Aged; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome; Triamcinolone; Trigger Finger Disorder
PubMed: 33849080
DOI: 10.1002/14651858.CD012789.pub2 -
Basic & Clinical Pharmacology &... Nov 2017Little is known about the course of the plasma concentration and the bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) contained in dermal patches. We... (Comparative Study)
Comparative Study Randomized Controlled Trial
Little is known about the course of the plasma concentration and the bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) contained in dermal patches. We compared an etofenamate prototype patch (patent EP 1833471) and a commercially available diclofenac epolamine patch regarding the bioavailability of the active ingredients relative to respective i.m. applications and regarding their plasma concentration-time course. Twenty-four healthy human volunteers were treated using a parallel group design (n = 12 per group) with a single dermal patch (removed after 12 hr) followed (after a latency of 48 hr) by eight consecutive dermal patches every 12 hr to reach steady-state conditions. The patches were generally well tolerated, but one volunteer treated with etofenamate developed an allergic contact dermatitis. After the first patch, C was 0.81 ± 0.11 (mean ± S.E.M.) ng/mL (reached 12 hr after patch removal) for diclofenac and 31.3 ± 3.8 ng/mL for flufenamic acid (reached at patch removal), the main metabolite of etofenamate. Etofenamate was not detectable. After repetitive dosing, trough plasma concentrations after the eighth dose were 1.72 ± 0.32 ng/mL for diclofenac and 48.7 ± 6.6 ng/mL for flufenamic acid. Bioavailabilities (single dose) relative to i.m. applications were 0.22 ± 0.04% for diclofenac and 1.15 ± 0.06% for flufenamic acid. In conclusion, the relative bioavailability (compared to the respective i.m. application) of both drugs is low. The maximal plasma concentrations after topical administration of these drugs are well below the IC values for COX-1 and COX-2, explaining the absence of dose-dependent toxicities.
Topics: Administration, Cutaneous; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Cross-Over Studies; Diclofenac; Drug Administration Schedule; Female; Flufenamic Acid; Humans; Inhibitory Concentration 50; Injections, Intramuscular; Male; Transdermal Patch; Young Adult
PubMed: 28561421
DOI: 10.1111/bcpt.12818 -
Biomedicine & Pharmacotherapy =... Mar 2019Topical formulations of non-steroidal anti-inflammatory drugs are often used to provide effective local drug concentration while limiting systemic exposure and...
Topical formulations of non-steroidal anti-inflammatory drugs are often used to provide effective local drug concentration while limiting systemic exposure and associated adverse events. Formulation composition has great influence on the rate of transdermal drug transport through human skin. This study was performed to compare the ex vivo transdermal transport of diclofenac from three topical formulations, a 1% liposomal gel formulation of diclofenac sodium and two emulsion gel formulations, 1.16% and 2.32% diclofenac diethylamine (equivalent to 1% and 2% diclofenac sodium). Human skin was obtained during unrelated surgical procedures and frozen at -20 °C until use. Three skin specimens were thawed, prepared for testing, and placed in a Franz cell with the stratum corneum facing the donor compartment. About 200 μl of each formulation was placed on the skin, and the receptor compartment fluid (phosphate buffered saline, pH 7.4, 32 °C) was sampled over the next 48 h. Diclofenac concentration was measured with a validated HPLC method. The transdermal permeability coefficient for the liposome 1% gel was 69.3 ± 14.4 10 cm•s, compared with 34.9 ± 9.1 10 cm•s (P = 0.001) and 47.1±9.5 10 cm•s (P = 0.005) for the emulsion gel 1.16% and emulsion gel 2.32%, respectively. A statistically significant difference between transdermal transport of diclofenac from the liposome gel 1% and the emulsion gel 1.16% was evident after 9 h, a clinically relevant result because these products are typically applied 2 to 4 times daily. Based on these observations, liposome gel 1% formulation of diclofenac may have a clinical advantage compared with the emulsion gel 1.16% formulation.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Compounding; Gels; Humans; Liposomes; Organ Culture Techniques; Skin; Skin Absorption
PubMed: 30612003
DOI: 10.1016/j.biopha.2018.12.079