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Frontiers in Microbiology 2023The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) has raised concerns regarding their environmental impact. To address this, understanding the effects...
INTRODUCTION
The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) has raised concerns regarding their environmental impact. To address this, understanding the effects of NSAIDs on bacteria is crucial for bioremediation efforts in pharmaceutical-contaminated environments. The primary challenge in breaking down persistent compounds lies not in the biochemical pathways but in capacity of bacteria to surmount stressors.
METHODS
In this study, we examined the biodegradative activity, morphological and physiological changes, and ultrastructural adaptations of strain IEGM 1243 when exposed to ibuprofen, diclofenac, and their mixture.
RESULTS AND DISCUSSION
Our findings revealed that IEGM 1243 exhibited moderate biodegradative activity towards the tested NSAIDs. Cellular respiration assay showed higher metabolic activity in the presence of NSAIDs, indicating their influence on bacterial metabolism. Furthermore, catalase activity in IEGM 1243 exposed to NSAIDs showed an initial decrease followed by fluctuations, with the most significant changes observed in the presence of DCF and the NSAID mixture, likely influenced by bacterial growth phases, active NSAID degradation, and the formation of multicellular aggregates, suggesting potential intercellular synergy and task distribution within the bacterial community. Morphometric analysis demonstrated alterations in size, shape, and surface roughness of cells exposed to NSAIDs, with a decrease in surface area and volume, and an increase in surface area-to-volume ratio (SA/V). Moreover, for the first time, transmission electron microscopy confirmed the presence of lipid inclusions, polyphosphates, and intracellular membrane-like structures in the ibuprofen-treated cells.
CONCLUSION
These results provide valuable insights into the adaptive responses of IEGM 1243 to NSAIDs, shedding light on the possible interaction between bacteria and pharmaceutical compounds in the environment.
PubMed: 38125575
DOI: 10.3389/fmicb.2023.1275553 -
Environmental Monitoring and Assessment Jul 2023The use of reclaimed water for crop irrigation presents a route through which pharmaceuticals enter the agro-environment, raising concerns about their potential...
The use of reclaimed water for crop irrigation presents a route through which pharmaceuticals enter the agro-environment, raising concerns about their potential inclusion into the food chain and associated health risks. The main objective of this study was to determine the accumulation of six pharmaceuticals (paracetamol, diclofenac and ibuprofen, ciprofloxacin, tetracycline, and sulfamethoxazole) in edible part of jute mallow (JM) (Corchorus olitorius) irrigated with treated hospital wastewater (THWW) and potential health risks associated with the consumption of the contaminated JM. In a greenhouse experiment, JM vegetable was grown in soils irrigated with groundwater and THWW. After 4 weeks of cultivation, the pharmaceutical concentrations in the soil and JM tissues were determined. The uptake and accumulation of the pharmaceuticals in the irrigated JM and the human health risks associated with their consumption were evaluated. Results showed that the THWW-irrigated and groundwater-irrigated soils accumulated all the studied pharmaceuticals except paracetamol and sulfamethoxazole, with the concentrations in the soil before and after irrigation ranging from 0.01 to 0.14 μg g and 0.03 to 1.35 μg g, respectively. In JM leaves, the accumulation was in the order of tetracycline > ciprofloxacin > ibuprofen > diclofenac and tetracycline > ciprofloxacin > diclofenac > ibuprofen under THWW-irrigated and groundwater-irrigated treatments, respectively. Under both treatments, the uptake and accumulation of the studied pharmaceuticals were in the order of roots > stem > leaves. The health risk assessment indicated that the consumption of the studied pharmaceuticals through JM implies some risks to human health and the risks were in the order of tetracycline > diclofenac > ciprofloxacin > ibuprofen > paracetamol > sulfamethoxazole. This study has demonstrated that irrigation with reclaimed water is a major route of pharmaceuticals into the food chain and a key determinant of associated health risks.
Topics: Humans; Wastewater; Corchorus; Agricultural Irrigation; Acetaminophen; Diclofenac; Ibuprofen; Environmental Monitoring; Risk Assessment; Anti-Bacterial Agents; Soil; Sulfamethoxazole; Ciprofloxacin; Water; Pharmaceutical Preparations; Tetracyclines; Soil Pollutants
PubMed: 37452922
DOI: 10.1007/s10661-023-11565-3 -
Journal of Enzyme Inhibition and... Dec 2023We designed and synthesised novel quinazolinone tethered phenyl urea derivatives () that triple target the double mutant EGFR, COX-2, and 15-LOX. Compounds (, , , , and...
Triple targeting of mutant EGFR, COX-2, and 15-LOX: design and synthesis of novel quinazolinone tethered phenyl urea derivatives for anti-inflammatory and anticancer evaluation.
We designed and synthesised novel quinazolinone tethered phenyl urea derivatives () that triple target the double mutant EGFR, COX-2, and 15-LOX. Compounds (, , , , and ) not only had low micromolar IC50 inhibitory activities against the three targets, but they also showed good selectivity for COX-2 over COX-1 and for EGFR over wild-type EGFR. Except for and , all of the tested compounds inhibited the NO production significantly more potently than celecoxib, diclofenac, and indomethacin. Compounds and reduced ROS levels more effectively than celecoxib and diclofenac. In terms of inhibiting TNF-α production, treated cells showed TNF-α level, which is ∼10 times lower than celecoxib. Furthermore, and had the highest anticancer activity against the breast cancer cell line BT-459 with growth inhibition percentages of 67.14 and 70.07%, respectively. Docking studies confirm their favoured binding affinity. The proposed compounds could be promising multi-targeted leads.
Topics: Humans; ErbB Receptors; Cyclooxygenase 2; Quinazolinones; Celecoxib; Diclofenac; Tumor Necrosis Factor-alpha; Lung Neoplasms; Protein Kinase Inhibitors; Mutation; Anti-Inflammatory Agents; Urea; Structure-Activity Relationship; Molecular Docking Simulation
PubMed: 37038884
DOI: 10.1080/14756366.2023.2199166 -
Cancers Oct 2023The use of topical and intralesional immunotherapy in the treatment of cutaneous malignant neoplasia in sensitive areas such as the lips and eyelids is discussed.... (Review)
Review
The use of topical and intralesional immunotherapy in the treatment of cutaneous malignant neoplasia in sensitive areas such as the lips and eyelids is discussed. Surgery may not be feasible or may result in deformities in these areas, making alternative treatment options necessary. A narrative literature review was conducted using MEDLINE (PubMed) as the main literature database, collecting available evidence of experiences with various topical and intralesional therapies in the aforementioned anatomical locations, ranging from case reports to clinical trials. The clearance rates and potential adverse reactions of therapeutic options such as imiquimod 5%, 5-fluorouracil (5-FU), photodynamic therapy (PDT), ingenol mebutate (IM), diclofenac, intralesional methotrexate, and interferon are reviewed. Although limited by their heterogeneity and the scarcity of clinical trials, these studies point towards promising response rates and minimal adverse effects, making these treatments viable options in selected cases.
PubMed: 37894385
DOI: 10.3390/cancers15205018 -
Veterinary Ophthalmology Oct 2023To evaluate the incidence, clinical features, treatment, and outcome of canine follicular conjunctivitis (CFC).
OBJECTIVE
To evaluate the incidence, clinical features, treatment, and outcome of canine follicular conjunctivitis (CFC).
PROCEDURE
Medical records of dogs diagnosed with CFC were reviewed. Data recorded included signalment, duration of clinical signs and treatment details prior to presentation, concurrent ocular/systemic diseases, ocular clinical signs, cytology, treatment, follow-up, and outcome. Blepharospasm, signs of self-trauma, hyperemia, chemosis, ocular discharge, and follicle location and severity (0.5-4) were retrospectively evaluated. Based on severity, treatment consisted of topical 0.1% diclofenac or 0.1% dexamethasone sodium eyedrops. Dogs were classified into young (YD < 18 months) and adult (AD ≥ 18 months).
RESULTS
One hundred and fifty-three dogs (276 eyes) were included in the study: 83YD (54%) and 70AD (46%). Males and bilateral disease were over-represented in both groups. Severity was associated with young age (p = .032) and bilaterality (p = .025), and not with dermatological diseases (p > .05). No differences in follicular location were observed except for more frequent involvement of the nictitating membrane (MN) in YD (p = .02). Response to treatment was faster in AD (p = .001), with complete resolution in 80.6% of the eyes (100/124) at 1 month. YD treated with diclofenac showed faster resolution than those treated with 0.1% dexamethasone (p = .009).
CONCLUSIONS
Although CFC is a bilateral ocular disease occurring at any age, the clinical presentation is influenced by age. Follicular conjunctivitis in adult dogs is less sever, less commonly affects the NM, and responds more quickly to topical treatment. One month of topical diclofenac may be adequate for mild cases, and 1 month of topical 0.1% dexamethasone is recommended as initial therapy for moderate to severely affected cases.
PubMed: 37850538
DOI: 10.1111/vop.13155 -
Nanomaterials (Basel, Switzerland) Dec 2023Pharmaceuticals and heavy metals pose significant risks to human health and aquatic ecosystems, necessitating their removal from water and wastewater. A promising...
Pharmaceuticals and heavy metals pose significant risks to human health and aquatic ecosystems, necessitating their removal from water and wastewater. A promising alternative for this purpose involves their removal by adsorption on composite sorbents prepared using a conventional layer-by-layer (LbL) method or an innovative coacervate direct deposition approach. In this study, four novel composite materials based on a silica core (IS) and a polyelectrolyte coacervate shell were used for the investigation of dynamic adsorption of three heavy metals (lead, nickel and cadmium) and an organic drug model (diclofenac sodium salt, DCF-Na). The four types of composite sorbents were tested for the first time in dynamic conditions (columns with continuous flow), and the column conditions were similar to those used in wastewater treatment plants. The influence of the polyanion nature (poly(acrylic acid) (PAA) vs. poly(sodium methacrylate) (PMAA)), maintaining a constant poly(ethyleneimine) (PEI), and the cross-linking degree (r = 0.1 and r = 1.0) of PEI chains on the immobilization of these pollutants (inorganic vs. organic) on the same type of composite was also studied. The experiments involved both single- and multi-component aqueous solutions. The kinetics of the dynamic adsorption process were examined using two non-linear models: the Thomas and Yoon-Nelson models. The tested sorbents demonstrated good adsorption capacities with affinities for the metal ions in the following order: Pb > Cd > Ni. An increase in the initial diclofenac sodium concentration led to an enhanced adsorption capacity of the IS/(PEI-PAA) sorbent. The calculated sorption capacities were in good agreement with the adsorption capacity predicted by the Thomas and Yoon-Nelson models. The substantial affinity observed between DCF-Na and a column containing composite microparticles saturated with heavy metal ions was explained.
PubMed: 38202488
DOI: 10.3390/nano14010033 -
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 -
International Journal of... May 2024This study explored the efficacy of activated carbon derived from rice straw and treated with ZnCl (ZnCl-RS) for the removal of diclofenac sodium (DCF) and paracetamol...
This study explored the efficacy of activated carbon derived from rice straw and treated with ZnCl (ZnCl-RS) for the removal of diclofenac sodium (DCF) and paracetamol (PCM) through an adsorption process. The investigation included examining the variations in removal efficiency at different pH levels and ZnCl-RS doses. The characteristics of the ZnCl-RS, prepared for the study, were determined through SEM and FTIR analyses, revealing a composition of 49.4% carbon and 8.3% zinc. At pH 5, the adsorption efficiency for DCF and PCM was enhanced, achieving removal rates of 92.2% for DCF and 89.1% for PCM with 0.2 g of ZnCl-RS. The adsorption of DCF and PCM by ZnCl-RS followed pseudo-second-order kinetic and adhered to the Langmuir isotherm model. The maximum adsorption capacities were calculated as 26.04 mg/g for DCF and 19.05 mg/g for PCM. In conclusion, the cost-effective production of activated carbon from agricultural waste like rice straw yielded a promising adsorbent material for efficiently removing pharmaceuticals such as diclofenac sodium and paracetamol. This approach not only contributes to waste reduction but also promotes the repurposing of agricultural waste materials.
PubMed: 38794784
DOI: 10.1080/15226514.2024.2357644 -
Naunyn-Schmiedeberg's Archives of... Oct 2023The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were...
The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were randomly distributed into six groups to treat inflammations of the colon, stomach, and small intestine caused by taking high doses of diclofenac (D), with two novel synthesized compounds, pyrazolo [3,4 d] pyridazine derivatives (Co1 and Co2). Myeloperoxidase enzyme activity was determined in the colon and small intestinal tissues. Serum contents of TNF-α, IL-22, IgG, and IgM were determined by ELISA. Histopathological examinations of the colon, small intestinal, and stomach tissues were microscopically analyzed. TNF-α, IL-22, and TNFSF11 gene expression were measured in the colon, intestinal, and spleen using qRT-PCR. Diclofenac caused surface columnar epithelial cell loss, focal necrosis of the gastric mucosa, inflammatory cell infiltration, and congested blood vessels in the stomach, colon, and small intestinal tissues. Co1 component was found to be better than Co2 component in reducing the focal necrosis of gastric mucosa and improving the histological structures of the stomach, colon, and small intestinal tissues. After 14 days, the activity of the myeloperoxidase enzyme was increased in group D and decreased in groups DCo1, DCo2, Co1, and Co2. Serum concentrations of TNF-α and IgG were increased, while IL-22 and IGM were reduced in the D, DCo1, and DCo2 groups compared with the Co1 and control groups. TNF-α gene was upregulated in the D group and downregulated in the Co1 group, while the IL-22 gene was downregulated in the D group and upregulated in the Co1 group compared with the control group. The CO1 component may be useful in reducing digestive system inflammation.
Topics: Mice; Animals; Colitis; Peroxidase; Tumor Necrosis Factor-alpha; Diclofenac; Carbon Dioxide; Intestinal Mucosa; Inflammation; Anti-Inflammatory Agents; Colon; Antioxidants; Necrosis; Immunoglobulin G; Immunoglobulin M; Disease Models, Animal
PubMed: 37126195
DOI: 10.1007/s00210-023-02493-7 -
Current Medical Research and Opinion Dec 2023Describe and characterize treatment patterns, satisfaction, improvement in pain and functional impairment (health-related quality of life [HRQoL]) in users of over the... (Observational Study)
Observational Study
Patients' experience and utilization patterns of diclofenac gel in Germany: a real-world study with a prospective longitudinal survey and a retrospective analysis of pharmacy data.
OBJECTIVE
Describe and characterize treatment patterns, satisfaction, improvement in pain and functional impairment (health-related quality of life [HRQoL]) in users of over the counter (OTC) Voltaren gel diclofenac (VGD) 2.32% and 1.16% in a real-world setting.
METHODS
This observational real-world German study had prospective and retrospective components. The prospective data were collected from electronic surveys completed by adults who purchased VGD to treat their musculoskeletal pain at baseline and 4 and 12 weeks after baseline. Retrospective data were from a 12-month (March 2019 to February 2020) abstraction from dispensing software platforms used in select German pharmacies.
RESULTS
Surveys from 467 participants (mean age 60.8 years) were analyzed. Average pain severity at baseline was 6.0 on an 11-point Numeric Rating Scale (0 = no pain, 10 = worst possible pain), improving by 0.8 and 1.2 points at Weeks 4 and 12, respectively. Performance of functional activities (daily/physical/social activities and errands/chores) improved and the proportion of participants with at least moderate interference decreased at both follow-up timepoints. Retrospective analyses indicated that majority of patients receiving VGD ( = 95,085) were ≥65 years old (67.9%), had one dispensed tube (70.8%) and did not switch to another topical treatment (including other NSAIDs) (77.3%), and were co-prescribed at least one cardiovascular medication (74.3%).
CONCLUSIONS
This study provides the first real-world insights into OTC VGD use in Germany. The participants using VGD reported a decrease in pain severity and an improvement of HRQoL while under treatment, as well as resulting satisfaction with treatment. Patients infrequently switched to alternate topical therapies/NSAIDs.
Topics: Adult; Humans; Middle Aged; Aged; Diclofenac; Retrospective Studies; Pharmacies; Prospective Studies; Quality of Life; Anti-Inflammatory Agents, Non-Steroidal; Longitudinal Studies; Chronic Pain; Pharmacy
PubMed: 37545357
DOI: 10.1080/03007995.2023.2243804