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1.
PeerJ ; 12: e18005, 2024.
Article in English | MEDLINE | ID: mdl-39221263

ABSTRACT

Background: Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac (DCF), form a significant group of environmental contaminants. When the toxic effects of DCF on plants are analyzed, authors often focus on photosynthesis, while mitochondrial respiration is usually overlooked. Therefore, an in vivo investigation of plant mitochondria functioning under DCF treatment is needed. In the present work, we decided to use the green alga Chlamydomonas reinhardtii as a model organism. Methods: Synchronous cultures of Chlamydomonas reinhardtii strain CC-1690 were treated with DCF at a concentration of 135.5 mg × L-1, corresponding to the toxicological value EC50/24. To assess the effects of short-term exposure to DCF on mitochondrial activity, oxygen consumption rate, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS) production were analyzed. To inhibit cytochrome c oxidase or alternative oxidase activity, potassium cyanide (KCN) or salicylhydroxamic acid (SHAM) were used, respectively. Moreover, the cell's structure organization was analyzed using confocal microscopy and transmission electron microscopy. Results: The results indicate that short-term exposure to DCF leads to an increase in oxygen consumption rate, accompanied by low MMP and reduced mtROS production by the cells in the treated populations as compared to control ones. These observations suggest an uncoupling of oxidative phosphorylation due to the disruption of mitochondrial membranes, which is consistent with the malformations in mitochondrial structures observed in electron micrographs, such as elongation, irregular forms, and degraded cristae, potentially indicating mitochondrial swelling or hyper-fission. The assumption about non-specific DCF action is further supported by comparing mitochondrial parameters in DCF-treated cells to the same parameters in cells treated with selective respiratory inhibitors: no similarities were found between the experimental variants. Conclusions: The results obtained in this work suggest that DCF strongly affects cells that experience mild metabolic or developmental disorders, not revealed under control conditions, while more vital cells are affected only slightly, as it was already indicated in literature. In the cells suffering from DCF treatment, the drug influence on mitochondria functioning in a non-specific way, destroying the structure of mitochondrial membranes. This primary effect probably led to the mitochondrial inner membrane permeability transition and the uncoupling of oxidative phosphorylation. It can be assumed that mitochondrial dysfunction is an important factor in DCF phytotoxicity. Because studies of the effects of NSAIDs on the functioning of plant mitochondria are relatively scarce, the present work is an important contribution to the elucidation of the mechanism of NSAID toxicity toward non-target plant organisms.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Chlamydomonas reinhardtii , Diclofenac , Membrane Potential, Mitochondrial , Mitochondria , Oxygen Consumption , Reactive Oxygen Species , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Diclofenac/toxicity , Chlamydomonas reinhardtii/drug effects , Chlamydomonas reinhardtii/metabolism , Chlamydomonas reinhardtii/ultrastructure , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Membrane Potential, Mitochondrial/drug effects , Oxygen Consumption/drug effects , Reactive Oxygen Species/metabolism , Electron Transport Complex IV/metabolism , Potassium Cyanide/toxicity , Oxidoreductases/metabolism , Salicylamides , Microscopy, Electron, Transmission , Plant Proteins , Mitochondrial Proteins
2.
Article in English | MEDLINE | ID: mdl-39225928

ABSTRACT

This work involved the preparation of pristine and iron nanoparticle-loaded biochar from a water chestnut shell to remove diclofenac sodium (DCF) containing effluent of pharmaceutical origin. To create suitable forecasting equations for the modelling of the DCF adsorption onto the adsorbent, response surface methodology (RSM) was used. The parameters, e.g. pH, adsorbent mass, DCF concentration and contact time, were used for the modeling of adsorption. The RSM model predicts that for 98.0% DCF removal, the ideal conditions are pH 6, an adsorbent dose of 0.5 g L-1, and a contact time of 60 min with an initial adsorbate concentration of 25 mg L-1 at 303 K. The maximum capacity deduced from the Langmuir model was 75.9 mg g-1 for pristine water chestnut shell biochar (pWCBC) and 122.3 mg g-1 for magnetically modified nano-Fe2O3 biochar (mWCBC). Under equilibrium conditions, the Langmuir model was the best-suited model compared to the Temkin and Freundlich models. The adsorption data in this investigation efficiently fitted the pseudo-second-order model, emphasizing that chemisorption or ion exchange processes may be involved in the process. The WCBC demonstrated recyclability after 10 cycles of repeated adsorption and desorption of DCF. A combined coagulation adsorption process removed COD, NH3-N, NO3-, PO43-, and DCF by 92.50%, 86.41%, 77.57%, 84.54%, and 97.25%, respectively. This study therefore shows that coagulation followed by adsorption onto biochar can be a cost-effective substitute for conventional pharmaceutical wastewater treatment.

3.
Dig Dis Sci ; 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39215866

ABSTRACT

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) carries a 3-15% risk of post-ERCP pancreatitis (PEP). Rectal indomethacin reduces the risk of PEP, but its cost has increased more than 20-fold over the past decade. Rectal diclofenac is also used to prevent PEP but is not commercially available in the United States. The aim of this study is to compare the incidence of PEP after administration of commercially available rectal indomethacin versus compounded rectal diclofenac and assess financial implications. METHODS: ERCP cases at our institution with administration of 100 mg rectal indomethacin or 100 mg compounded rectal diclofenac between May 2018 and January 2022 were retrospectively reviewed. The incidence and severity of PEP was compared between the indomethacin (n = 728) and diclofenac (n = 304) groups. Risk factors (young age, female sex, history of pancreatitis or PEP, sphincterotomy during procedure, pancreatic indication, trainee involvement) and protective factors (prior sphincterotomy, pancreatic duct stenting) for PEP were compared between groups. RESULTS: 60 patients (8.2%) in the rectal indomethacin group and 25 patients (8.2%) in the compounded rectal diclofenac group developed PEP, resulting in moderate or severe PEP in 9 (15.0%) and 2 (8.0%) patients, respectively. The compounded rectal diclofenac group had more trainee involvement (46.1% vs. 32.8%, p = 0.0001) and more prior sphincterotomy cases (15.8% vs. 10.6%, p = 0.0193) compared to the rectal indomethacin group; no statistically significant differences were observed in all other risk and protective factors. Following switch to compounded rectal diclofenac, institutional annual cost savings amounted to $441,460.62 and patient charge decreased 45-fold. CONCLUSION: This retrospective single-center real-world analysis showed similar efficacy of rectal indomethacin and compounded rectal diclofenac in preventing PEP but demonstrates substantial cost savings after switching to compounded rectal diclofenac.

4.
Sci Rep ; 14(1): 19009, 2024 08 16.
Article in English | MEDLINE | ID: mdl-39152164

ABSTRACT

The contamination of water sources by pharmaceutical pollutants presents significant environmental and health hazards, making the development of effective photocatalytic materials crucial for their removal. This research focuses on the synthesis of a novel Ag/CuS/Fe3O4 nanocomposite and its photocatalytic efficiency against tetracycline (TC) and diclofenac contaminants. The nanocomposite was created through a straightforward and scalable precipitation method, integrating silver nanoparticles (AgNPs) and copper sulfide (CuS) into a magnetite framework. Various analytical techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR),ultraviolet-visible spectrophotometry (UV-Vis) and energy-dispersive X-ray spectroscopy (EDS), were employed to characterize the structural and morphological properties of the synthesized material. The photocatalytic activity was tested by degrading tetracycline and diclofenac under visible light. Results indicated a marked improvement in the photocatalytic performance of the Ag/CuS/Fe3O4 nanocomposite (98%photodegradation of TC 60 ppm in 30 min) compared to both pure magnetite and CuS/Fe3O4. The enhanced photocatalytic efficiency is attributed to the synergistic interaction between AgNPs, CuS, and Fe3O4, which improves light absorption and charge separation, thereby increasing the generation of reactive oxygen species (ROS) and promoting the degradation of the pollutants. The rate constant k of photodegradation was about 0.1 min-1 for catalyst dosages 0.02 g. Also the effect of photocatalyst dose and concentration of TC and pH of solution was tested. The modified photocatalyst was also used for simultaneous photodegradation of TC and diclofenac successfully. This study highlights the potential of the Ag/CuS/Fe3O4 nanocomposite as an efficient and reusable photocatalyst for eliminating pharmaceutical pollutants from water.


Subject(s)
Copper , Diclofenac , Ferrosoferric Oxide , Nanocomposites , Silver , Tetracycline , Water Pollutants, Chemical , Diclofenac/chemistry , Nanocomposites/chemistry , Tetracycline/chemistry , Catalysis , Silver/chemistry , Ferrosoferric Oxide/chemistry , Water Pollutants, Chemical/chemistry , Copper/chemistry , Metal Nanoparticles/chemistry , Photolysis , X-Ray Diffraction , Light
5.
Cell Biochem Biophys ; 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39127861

ABSTRACT

Nephrotoxicity is a common side effect arising from exposure to drugs or toxins. The study investigates the therapeutic effects of Thunbergia alata and Thunbergia erecta flowers on diclofenac-induced renal injury. Secondary metabolite characterization by positive mode high-resolution-ESI (LC-HR-ESI-MS) was followed by assessing their renal protection against diclofenac-induced damage and molecular docking studies. Using positive LC-HR-ESI-MS, 18 compounds from T. erecta and T. alata were identified. Diclofenac administration induced significant deterioration of all parameters in the kidney in addition to renal tissue contents of several inflammatory markers. The flower extracts of T. alata and T. erecta showed a clear improvement in the treated groups compared to the diclofenac-control group. The results were confirmed by histopathological examinations followed by immunohistochemical determination of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2-related factor 2 (Nrf2), and transforming growth factor beta 1 (TGF-ß1) expression. Furthermore, a protein-protein network to understand the complex interplay between the target proteins and their counterparts was done in addition to a molecular docking study of the de-replicated compounds in the active sites of NF-κB, TGF-ß1, and VEGFR.

6.
Cureus ; 16(7): e64452, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39135838

ABSTRACT

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for various conditions but are associated with numerous adverse drug reactions (ADRs). Understanding these ADRs is necessary to reduce morbidity and mortality. NSAID-induced angioedema, although rare, can be life-threatening and is often due to increased leukotriene production from COX pathway inhibition. Mast cells and basophil degranulation play vital roles in its pathogenesis. Prompt recognition and immediate cessation of the culprit drug, along with the administration of corticosteroids and antihistamines, are essential. Here, we report a case of angioedema caused by diclofenac administration, which needs prompt vigilance and a rapid therapeutic response.

7.
Int J Biol Macromol ; 278(Pt 3): 134871, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39173807

ABSTRACT

Pharmaceuticals and personal care products and dyes have low biodegradability and high toxicity, seriously threaten the human health and ecological environment. Therefore, seeking effective removal methods has become the focus of research. In this study, silver-based metal-organic framework (Ag-MOF) and chitosan (CS) hybrid adsorbent (Ag-MOF-CS) was synthesized via solvothermal one-pot synthesis to remove diclofenac sodium (DCF) and acid Red 1 (AR1) from water for the first time. The morphology and structure of Ag-MOF-CS were confirmed by various characterizations. The effect on adsorption was investigated by changing the adsorbent dosage, pH and other conditions. The adsorption kinetics, adsorption isotherms and thermodynamics were analyzed. Ag-MOF-CS showed a high adsorption capacity. And the maximum adsorption capacity of Ag-MOF-CS for DCF and AR1 was 351.75 mg/g and 678.83 mg/g, respectively. The adsorbent bound to DCF and AR1 may via electrostatic forces, π-π interactions, hydrogen bonding. Even after four cycles of Ag-MOF-CS, the DCF removal can still be higher than 80 %. The eco-friendly Ag-MOF-CS demonstrated significant potential for utilization in treating wastewater.

8.
Int J Biol Macromol ; 279(Pt 1): 135161, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39214200

ABSTRACT

Diclofenac (DCF) is frequently detected in aquatic environments, emphasizing the critical need for its efficient removal globally. Here, we present the synthesis of Fe(III)-doped ß-CD-grafted chitosan (Fe/ß-CD@CS) cryogel beads designed for adsorbing DCF in aqueous solutions. The beads exhibited an average size of 2.94 ± 0.66 mm and a point of zero charge of 8.03. Adsorption experiments demonstrated that the Langmuir kinetic model provided the most accurate description of the kinetic data, while the Redlich-Peterson isotherm offered the best fit for the equilibrium data. The beads showcased a theoretical maximum adsorption capacity of 712.3 mg/g for DCF, with the adsorption process being identified as exothermic. DCF adsorption on the beads was attributed to hydrogen bonding, metal cation-π interactions, and electrostatic interactions. Reusability tests exhibited that the beads could be regenerated using 0.1 M NaOH. To perform deep learning modeling, adsorption experiments (n = 17), designed utilizing central composite design (CCD), were conducted in duplicate. The CCD framework incorporated input variables such as initial DCF concentration, adsorbent dosage, and solution pH, while the output variable was the DCF removal rate. Utilizing the adsorption data, an artificial neural network (ANN) model was constructed with a topology of 3: 7:10:1, featuring 3 input variables, 7 neurons in the first hidden layer, 10 neurons in the second layer, and 1 output variable. Employing the ANN model data, 3-D response surface plots were generated to elucidate the relationship between input variables and DCF removal rate. Additional adsorption tests were conducted to evaluate the developed ANN model, affirming its reliable predictability for the DCF removal rate. Analysis of the relative importance of the input variables revealed the following order of importance: solution pH (100 %) > adsorbent dosage (75.2 %) > initial DCF concentration (57.7 %).

9.
Plants (Basel) ; 13(16)2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39204625

ABSTRACT

Diclofenac, often detected in environmental samples, poses a potential hazard to the aquatic environment. The present study aimed to understand the effect of this drug on photosynthetic apparatus, which is a little-known aspect of its phytotoxicity. Chloroplasts and thylakoids isolated from spinach (Spinacia oleracea) were used for this study and treated with various concentrations of diclofenac (from 125 to 4000 µM). The parameters of chlorophyll a fluorescence (the OJIP test) as measurements for both the intact chloroplasts and the thylakoid membranes revealed that isolated thylakoids showed greater sensitivity to the drug than chloroplasts. The relatively high concentration of diclofenac that is required to inhibit chloroplast and thylakoid functions suggests a narcotic effect of that drug on photosynthetic membranes, rather than a specific interaction with a particular element of the electron transport chain. Using confocal microscopy, we confirmed the degradation of the chloroplast structure after DCF treatment, which has not been previously reported in the literature. In conclusion, it can be assumed that diclofenac's action originated from a non-specific interaction with photosynthetic membranes, leading to the disruption in the function of the electron transport chain. This, in turn, decreases the efficiency of photosynthesis, transforming part of the PSII reaction centers into heat sinks and enhancing non-photochemical energy dissipation.

10.
Life Sci ; 353: 122936, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39094904

ABSTRACT

Diclofenac (DF), a non-steroidal anti-inflammatory drug, is commonly used to relieve pain and inflammation. High doses of DF might induce acute kidney injury (AKI), particularly in elderly, a known vulnerable population. AIM: We aimed to assess the protective role of melatonin (Mel) on DF-induced AKI in aged rats and to highlight the underpinning mechanisms include, oxidative stress and inflammation focusing on microRNA-34a (miR-34a), nuclear factor erythroid-2-related factor-2/hemeoxygenase-1 (Nrf2/HO-1) and NLR family-pyrin domain containing-3 (NLRP3) inflammasome pathways, and to elucidate the possibility of epithelial sodium channel (ENaC) involvement. MATERIALS AND METHODS: Thirty old male Wistar rats were allocated randomly into 3 groups: Control, DF and Mel-DF groups. KEY FINDINGS: Melatonin provided nephroprotective effects against DF-induced AKI via attenuating the expression of renal miR-34a and subsequently promoting the signaling of Nrf2/HO-1 with elevation of the antioxidant defense capacity and suppressing NLRP3 inflammasomes. Melatonin alleviated DF-induced hypernatremia via decreasing the ENaC expression. Renal histopathological examination revealed significant reduction in vascular congestion, mononuclear infiltration, glomerulo-tubular damage, fibrosis and TNF-α optical density. SIGNIFICANCE: It can be assumed that melatonin is a promising safe therapeutic agent in controlling DF-induced AKI in elderly.


Subject(s)
Acute Kidney Injury , Anti-Inflammatory Agents, Non-Steroidal , Diclofenac , Melatonin , Oxidative Stress , Rats, Wistar , Animals , Melatonin/pharmacology , Melatonin/therapeutic use , Male , Acute Kidney Injury/metabolism , Acute Kidney Injury/prevention & control , Acute Kidney Injury/chemically induced , Acute Kidney Injury/drug therapy , Acute Kidney Injury/pathology , Rats , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Oxidative Stress/drug effects , Antioxidants/pharmacology , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NF-E2-Related Factor 2/metabolism , Protective Agents/pharmacology , Kidney/drug effects , Kidney/pathology , Kidney/metabolism
11.
Chemosphere ; 364: 142989, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39098350

ABSTRACT

Diclofenac (DLF), a widely recognized non-steroidal anti-inflammatory drug (NSAID), and sulfamethoxazole (SMX), a broad-spectrum sulfonamide antibiotic, are commonly prescribed medications that have raised concerns as significant contributors to pharmaceutical pollution in natural ecosystems despite their clinical effectiveness. This study investigates the potential phytoremediation pathways for these two drugs in plant systems by tracking and quantifying the fate of the parent compounds and their metabolites in Arabidopsis thaliana using cell and seedling cultures. Results indicated significant differences in the dissipation of DLF according to the treatment and time interaction within the cell cultures. Viable plant cells showed complete dissipation of DLF from an initial concentration of 2758 ng/mL in 96 h, whereas non-viable cells and blank solutions remained stable. The dissipation of SMX was comparable across viable, non-viable, and blanks, showing a minor decrease from 842 to 799 ng/mL over 120 h following the treatment of viable cells. DLF metabolites including 4'-hydroxy-diclofenac, 5-hydroxy-diclofenac, acyl-glutamatyl-diclofenac, 1-(2,6-dichlorophenyl)-5-hydroxy-2-indolinone, 5-sulfooxy-diclofenac, 5-glucopyranosyloxy-diclofenac, 1-(2,6-dichloro-4-hydroxyphenyl)-2-indolinone, and 4'-glucopyranosyloxy-diclofenac were recognized, likely formed through acylation, glutamyl conjugation, hydroxylation, dehydration, cyclization, sulfonation, and glucosidation. While for SMX, metabolites including sulfamethoxazole-glucuronide, nitroso-sulfamethoxazole, N4-acetylsulfamethoxazole, and N4-acetyl-5-OH-sulfamethoxazole were identified, potentially produced through glucuronidation, nitrosation, acetylation, and hydroxylation. Phase I metabolite concentrations of DLF and SMX peaked earlier than those of phase II metabolites. Hydroponic A. thaliana demonstrated comparable efficiencies in the phytoremediation of DLF and SMX, with concentrations varying from 1 mg/L to 10 mg/L. Detectable levels of both parent compounds and their metabolites confirmed successful absorption and metabolism within the plant system. This study provides valuable insights into the potential of phytoremediation as a sustainable approach for reducing the environmental toxicity of DLF and SMX and suggests comparable metabolic efficiency. These findings contribute to the growing body of knowledge on phytoremediation and its application in addressing pollution from pharmaceuticals and personal care products.

12.
Sci Total Environ ; 950: 174915, 2024 Nov 10.
Article in English | MEDLINE | ID: mdl-39134262

ABSTRACT

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used pharmaceuticals. Their presence in natural waters is due to the low removal efficiency in conventional wastewater treatment plants (WWTPs). Interestingly, certain zooplankton species can survive the mixture of pollution and abnormal water conditions in WWTPs. In our study, for the first time, we tested the in-situ bioaccumulation of NSAIDs and their metabolites in Daphnia pulex, which were obtained in high numbers in one WWTP during the summer. It was found that diclofenac (DCF) and 4-hydroxy DCF were present in the studied clarifiers and ponds. Among these chemicals, only DCF was detected in daphnia. The bioaccumulation factor of DCF in daphnia was below 36 L kg-1ww and was lower than those obtained under experimental conditions for Daphnia magna. The tested daphnia adapted to chronic exposure to mixtures of drugs in µg L-1 level and could be implemented in biobased WWTPs. According to our data, there is a need to supplement the risk assessment of anthropogenic pollutants with in-situ cases to demonstrate the adaptation possibilities of wild-living organisms.


Subject(s)
Bioaccumulation , Daphnia , Environmental Monitoring , Waste Disposal, Fluid , Wastewater , Water Pollutants, Chemical , Animals , Daphnia/metabolism , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/metabolism , Wastewater/chemistry , Waste Disposal, Fluid/methods , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/analysis
13.
Scand J Pain ; 24(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-39175232

ABSTRACT

OBJECTIVES: The aim of this study was to understand profiles of topical Voltaren gel diclofenac (VGD) 2.32 and 1.16% consumers through analyzing prescription patterns and to characterize treatment satisfaction, functional impairment, and pain relief after over-the-counter (OTC) VGD use in Sweden under real-world conditions. METHODS: This observational, real-world study conducted in Sweden had retrospective and prospective segments. The retrospective secondary data segment utilized 12-month diclofenac gel prescription data from the Swedish eHealth Agency (E-hälsomyndigheten). The prospective segment included electronic surveys completed at baseline and weeks 4 and 12 by adult consumers who purchased OTC VGD to treat their pain. RESULTS: Secondary data analyses (n = 12,145) showed that 56.7% of patients receiving diclofenac gel were females ≥70 years old. Most patients did not switch pain treatments; the mean time between diclofenac gel refills was about 2.5 months. From the surveys (n = 264), VGD provided pain relief, indicated by improvement in 11-point pain numeric rating scale scores. Average pain severity at baseline was 5.8 - improving by a mean of 1.3 and 1.9 points at weeks 4 and 12, respectively. The majority of consumers reported improvement in daily functioning (i.e., health-related quality of life [HRQoL]), and most were at least somewhat satisfied with VGD treatment results. CONCLUSIONS: This real-world study provides important insights into the prescription patterns of diclofenac gel and the consumer experience with OTC VGD in Sweden. Patients rarely switched to other topical nonsteroidal anti-inflammatory drugs, and VGD consumers reported pain relief and improved HRQoL compared to baseline - resulting in treatment satisfaction.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Diclofenac , Gels , Patient Satisfaction , Humans , Diclofenac/administration & dosage , Diclofenac/therapeutic use , Female , Sweden , Male , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Middle Aged , Aged , Adult , Retrospective Studies , Prospective Studies , Nonprescription Drugs/therapeutic use , Nonprescription Drugs/administration & dosage , Pain/drug therapy
14.
Anticancer Res ; 44(9): 3793-3798, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39197907

ABSTRACT

BACKGROUND/AIM: Nitric oxide (NO) has various physiological activities. In this study, diclofenac (DF) which has a high affinity for human serum albumin (HSA) was nitrosylated to a novel NO donor (NDF). The cytotoxic effects and the mechanism of NDF were investigated. MATERIALS AND METHODS: Binding experiments of NDF to HSA were performed by the ultrafiltration method. NO was measured by the Griess method. The number of dead cells were measured using annexin V. Apoptosis and endoplasmic reticulum stress were evaluated by western blotting. RESULTS: NDF competitively inhibits the binding of DF to HSA, suggesting that NDF and DF have equivalent binding characteristics. NDF rapidly released NOx after being dissolved. At 200 µM, NDF induced cell death in human pancreatic cancer cells. Western blotting showed that NDF promoted the cleavage of PARP, caspase-3, and caspase-7. Inhibitors of caspase-1 and caspase-9 significantly suppressed NDF-induced cell death, as did a non-specific caspase inhibitor (Z-VAD). In addition, NDF significantly increased the expression of the endoplasmic reticulum stress marker, CHOP. CONCLUSION: NDF induces apoptotic cell death by causing endoplasmic reticulum stress. The findings of this study suggest that NDF may become a promising compound for the treatment of pancreatic cancer.


Subject(s)
Apoptosis , Diclofenac , Endoplasmic Reticulum Stress , Nitric Oxide Donors , Pancreatic Neoplasms , Humans , Endoplasmic Reticulum Stress/drug effects , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/drug therapy , Diclofenac/pharmacology , Cell Line, Tumor , Apoptosis/drug effects , Nitric Oxide Donors/pharmacology , Nitric Oxide/metabolism , Serum Albumin, Human/metabolism , Cell Death/drug effects
15.
Eur J Obstet Gynecol Reprod Biol X ; 23: 100326, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39104867

ABSTRACT

Objective: To determine the efficacy and safety of rectal diclofenac for relieving postoperative pain following diagnostic hystero-laparoscopy and dye test (dHLD). Methods: A prospective, double-blind, placebo-controlled, randomized trial was conducted among women who underwent dHLD to evaluate fertility. The women received either rectal diclofenac with intramuscular pentazocine or intramuscular pentazocine with rectal placebo for postoperative analgesia. The median pain scores at different time points were assessed as the primary outcome measures using the Numerical Rating Scale for pain. The secondary outcome measures were analgesic consumption, time at which first analgesic was requested, satisfaction with pain relief and any adverse events. Results: In total, 108 participants were analysed (54 in each group, 1:1 ratio). The median score for postoperative pain was lower for the diclofenac group compared with the placebo group at 4 h (52.53 vs 56.47; p = 0.507), 6 h (50.48 vs 58.52; p = 0.174), 8 h (51.42 vs 57.65; p = 0.296), 10 h (51.35 vs 57.65; p = 0.285) and 12 h (52.45 vs 56.55; p = 0.485) post surgery, although the difference was not significant (p > 0.05). Seventeen participants required rescue analgesia with 30 mg of pentazocine: 11 at 4 h post surgery [5 (62.5 %) vs 6 (66.7 %)], three at 6 h post surgery [2 (25.0 %) vs 1 (11.1 %)], two at 8 h post surgery [1 (12.5 %) vs 1 (11.1 %)], and one at 12 h post surgery [0 vs 1 (11.1 %)] for the diclofenac and placebo groups respectively (p = 0.713). There were no significant differences in postoperative adverse effect profiles, overall patient satisfaction, and need for rescue analgesia between the two groups (p > 0.05). Conclusions: Postoperative use of rectal diclofenac and pentazocine is safe, but did not significantly improve pain scores, patient satisfaction and need for rescue analgesia following dHLD, compared with patients who received pentazocine and placebo. While a multi-modal approach to pain relief following dHLD does not appear to be significantly beneficial, a multi-centre study is needed to confirm or refute these findings.

16.
ChemMedChem ; : e202400321, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39087920

ABSTRACT

Hearing loss (HL) affects more than 5% of the global population, with projections indicating an impact of up to 50% on young individuals in the next years. HL treatments remain limited due to the inner ear's hermeticism. HL often involves inflammatory processes, underscoring the need for enhanced delivery of antiinflammatory agents to the inner ear. Our research focuses on the development of a directed therapy based on magnetic nanoparticles (MNPs). We previously synthesized biocompatible folic acid-coated iron oxide-core nanoparticles (MNPs@FA) as potential carriers for the anti-inflammatory Diclofenac (Dfc). This study aims to incorporate Dfc onto MNPs@FA to facilitate targeted drug delivery to the inner ear. Through optimizing the loading procedure, we achieved optimal loading capacity. Dfc release was studied in the simulated target fluid and the administration vehicle. Complete characterization is also shown. In vitro biocompatibility testing ensured the biosafety of the resulting formulation. Subsequent ex vivo targeting assays on murine cochleae validated the nanosystems' ability to penetrate the round window membrane, one of the main HL therapy barriers. These findings serve as validation before continuing to more complex in vivo studies. Together, the data here presented represent an advancement in addressing unmet medical needs in HL therapy.

17.
Materials (Basel) ; 17(15)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39124348

ABSTRACT

The presence of pharmaceuticals or their active metabolites in receiving waters is a sign of the inefficient removal of bioactive substrates from wastewater. Adsorption seems to be the most effective and inexpensive method of their removal. Waste management aimed at sorbents is a promising way to sustain several sustainable development goals. In the presented paper, the removal of the two most widely used drugs in the wastewater was examined. Diclofenac and carbamazepine were removed from water and wastewater using textile waste-derived sorbents. Their removal efficiency was verified by testing several process parameters such as the time of the sorption, the presence of interfering inorganic ions, the presence of dissolved organic matter, the initial pH and ionic strength of the solution, and various water matrices. The adsorption capacity was noted for diclofenac (57.1 mg/g) and carbamazepine (21.25 mg/g). The tested process parameters (pH, presence of inorganic ions, dissolved organic matter, ionic strength, water matrix) confirmed that the presented waste materials possessed a great potential for pharmaceutical removal from water matrices.

18.
Article in English | MEDLINE | ID: mdl-39172341

ABSTRACT

Herein, we report the efficient photocatalytic degradation of the diclofenac drug using the Zn1-x-yPrxAlyO photocatalyst [x, y] = (0.00, 0.00), (0.03, 0.01), (0.03,0.03) under UV light irradiation. The analysis of the structure reveals that the Pr3+ and Al3+ cations insertion into the ZnO lattice leads to a decrease in the lattice constant (a and c), Zn-O bond length, strain lattice, and crystallite size. These alterations are linked to the high degree of atomic disorder triggered by the dopants, which produce stress and strain in the ZnO structure. The Raman measurements confirmed the structural phase and showed changes in the position and intensity of the E2High mode, associated with oxygen vibrations and material crystallinity. The presence of the dopants reduces the concentration of VZn and VO++ type defects while increasing the levels of VO, VO+, and Oi defects, as observed from the fitting of the Photoluminescence spectra. Furthermore, it was noted that de Pr3+ and Al3+ cations insertion into ZnO increases the optical band gap, which is associated with the Moss-Burstein effect. The micrograph images show that dopants transform the morphology from quasi-spherical particles to irregular cluster structures. The textural analysis indicated that an increase in the concentration of Al3+ in the ZnO lattice led to a higher surface area, likely enhancing photocatalytic activity. The sample containing 3% Pr3+ and 3% Al3+ showed the highest photocatalytic activity and degraded up to 71.42% of diclofenac. In addition, experiments with scavengers revealed that hydroxyl radicals are the main species involved in the drug's photodegradation mechanism. Finally, the Zn1-x-yPrxAlyO compound is highly recyclable and stable.

19.
Environ Monit Assess ; 196(9): 802, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120741

ABSTRACT

This study assess how well diclofenac (DCF) can be separated from aqueous solution using potassium permanganate-modified eggshell biosorbent (MEB). The MEB produced was characterised using XRD, FTIR, and SEM. Batch experiments were conducted to examine and assess the impact of contact time, adsorbent dosage, initial concentration, and temperature on the adsorption capacity of the MEB in the DCF sequestration. The best parameters to obtained 95.64% DCF removal from liquid environment were 0.05 g MEB weight, 50 mg/L initial concentration, and 60 min contact time at room temperature. The maximum DCF sequestration capacity was found to be 159.57 mg/g with 0.05 g of MEB at 298 K. The adsorption isotherm data were more accurately predicted by the Freundlich model, indicating a process of heterogeneous multilayer adsorption. The results of the kinetic study indicated that the pseudo-second-order kinetic models best matched the experimental data. The findings revealed that the dynamic of DCF entrapment is largely chemisorption and diffusion controlled. Based on the values of thermodynamic parameters, the process is both spontaneous and endothermic. The primary processes of DCF sorption mechanism onto the MEB were chemical surface complexation, hydrogen bonding, π-π stacking, and electrostatic interactions. The produced MEB showed effective DCF separation from the aqueous solution and continued to have maximal adsorption capability even after five regeneration cycles. These findings suggest that MEB could be highly efficient adsorbent for the removal of DCF from pharmaceutical wastewater.


Subject(s)
Diclofenac , Egg Shell , Potassium Permanganate , Thermodynamics , Water Pollutants, Chemical , Diclofenac/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Adsorption , Kinetics , Egg Shell/chemistry , Potassium Permanganate/chemistry , Water Purification/methods , Waste Disposal, Fluid/methods , Animals
20.
Chemosphere ; 363: 142974, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39084301

ABSTRACT

The prevalent presence of pharmaceuticals in aquatic ecosystems underscores the necessity for developing cost-effective techniques to remove them from water. The utilization of affordable precursors in producing activated carbon, capable of rivaling commercial alternatives, remains a persistent challenge. The adsorption of diclofenac and ciprofloxacin onto a novel pinewood-derived activated carbon (FPWAC) was explored, employing a sequential activation process involving ammonium nitrate (NH4NO3) treatment followed by sodium hydroxide (NaOH) activation. The produced FPWAC was then thoroughly characterized by employing several techniques. The removal of diclofenac and ciprofloxacin in water and real wastewater effluent was examined in batch tests. The optimum removal conditions were an FPWAC dosage of 1 g L-1, pH 6, mixture concentration of 25 mg L-1, and a temperature of 25 °C. The FPWAC was able to remove both pharmaceuticals for up to six cycles, with more than 95% removal for water and 90% for wastewater in the first cycle. The adsorption performance fitted well with the non-linear Freundlich isotherm for both pollutants. The kinetics of adsorption of diclofenac followed a pseudo-first-order model, while ciprofloxacin showed adherence to the pseudo-second-order model. FPWAC proved its potency as a low-cost adsorbent for pharmaceutical removal from wastewater.


Subject(s)
Ciprofloxacin , Diclofenac , Wastewater , Water Pollutants, Chemical , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Wastewater/chemistry , Diclofenac/chemistry , Diclofenac/isolation & purification , Diclofenac/analysis , Adsorption , Ciprofloxacin/chemistry , Ciprofloxacin/isolation & purification , Ciprofloxacin/analysis , Water Purification/methods , Waste Disposal, Fluid/methods , Pinus/chemistry , Charcoal/chemistry , Wood/chemistry , Kinetics , Hydrogen-Ion Concentration
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