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Journal of Hazardous Materials Jun 2024The cyanobacterial response to pharmaceuticals is less frequently investigated compared to green algae. Pharmaceuticals can influence not only the growth rate of...
The cyanobacterial response to pharmaceuticals is less frequently investigated compared to green algae. Pharmaceuticals can influence not only the growth rate of cyanobacteria culture, but can also cause changes at the cellular level. The effect of diclofenac (DCF) as one of the for cyanobacteria has been rarely tested, and DCF has never been applied with cellular biomarkers. The aim of this work was to test the response of two unicellular cyanobacteria (Synechocystis salina and Microcystis aeruginosa) toward DCF (100 mg L) under photoautotrophic growth conditions. Such endpoints were analyzed as cells number, DCF uptake, the change in concentrations of photosynthetic pigments, the production of toxins, and chlorophyll a in vivo fluorescence. It was noted that during a 96 h exposure, cell proliferation was not impacted. Nevertheless, a biochemical response was observed. The increased production of microcystin was noted for M. aeruginosa. Due to the negligible absorption of DCF into cells, it is possible that the biochemical changes are induced by an external signal. The application of non-standard biomarkers demonstrates the effect of DCF on microorganism metabolism without a corresponding effect on biomass. The high resistance of cyanobacteria to DCF and the stimulating effect of DCF on the secretion of toxins raise concerns for environment biodiversity.
Topics: Microcystis; Diclofenac; Biomarkers; Synechocystis; Chlorophyll A; Microcystins; Chlorophyll; Water Pollutants, Chemical; Photosynthesis; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38678710
DOI: 10.1016/j.jhazmat.2024.134373 -
Chemosphere Jun 2024The treatment of waterborne micropollutants, such as diclofenac, presents a significant challenge to wastewater treatment plants due to their incomplete removal by...
The treatment of waterborne micropollutants, such as diclofenac, presents a significant challenge to wastewater treatment plants due to their incomplete removal by conventional methods. Ozonation is an effective technique for the degradation of micropollutants. However, incomplete oxidation can lead to the formation of ecotoxic by-products that require a subsequent post-treatment step. In this study, we analyze the susceptibility of micropollutant ozonation products to enzymatic digestion with laccase from Trametes versicolor to evaluate the potential of enzymatic treatment as a post-ozonation step. The omnipresent micropollutant diclofenac is used as an example, and the enzymatic degradation kinetics of all 14 detected ozonation products are analyzed by high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-HRMS) and tandem mass spectrometry (MS). The analysis shows that most of the ozonation products are responsive to chemo-enzymatic treatment but show considerable variation in enzymatic degradation kinetics and efficiencies. Mechanistic investigation of representative transformation products reveals that the hydroxylated aromatic nature of the ozonation products matches the substrate spectrum, facilitating their rapid recognition as substrates by laccase. However, after initiation by laccase, the subsequent chemical pathway of the enzymatically formed radicals determines the global degradability observed in the enzymatic process. Substrates capable of forming stable molecular oxidation products inhibit complete detoxification by oligomerization. This emphasizes that it is not the enzymatic uptake of the substrates but the channelling of the reaction of the substrate radicals towards the oligomerization of the substrate radicals that is the key step in the further development of an enzymatic treatment step for wastewater applications.
Topics: Diclofenac; Laccase; Ozone; Water Pollutants, Chemical; Wastewater; Oxidation-Reduction; Kinetics; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Waste Disposal, Fluid; Water Purification; Polyporaceae
PubMed: 38677613
DOI: 10.1016/j.chemosphere.2024.142112 -
Marine Drugs Mar 2024Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Y39-2. The...
Marine natural products are important sources of novel drugs. In this study, we isolated 4-hydroxyphenylacetic acid (HPA) from the marine-derived fungus Y39-2. The antithrombotic activity and mechanism of HPA were reported for the first time. Using a zebrafish model, we found that HPA had a strong antithrombotic activity because it can significantly increase cardiac erythrocytes, blood flow velocity, and heart rate, reduce caudal thrombus, and reverse the inflammatory response caused by Arachidonic Acid (AA). Further transcriptome analysis and qRT-PCR validation demonstrated that HPA may regulate autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway to exert antithrombotic effects.
Topics: Animals; Zebrafish; Phenylacetates; Autophagy; Fibrinolytic Agents; Signal Transduction; Biological Products; Thrombosis; Disease Models, Animal; Aquatic Organisms
PubMed: 38667765
DOI: 10.3390/md22040148 -
Journal of Controlled Release :... Jun 2024The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile...
The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile accessibility to the population. New drug delivery systems (DDS) are necessary to overcome the bioavailability and toxicity related to NSAIDs. In this context, UiO-66(Zr) metal-organic framework (MOF) shows high porosity, stability, and load capacity, thus being a promising DDS. However, the adsorption and release capability for different NSAIDs is scarcely described. In this work, the biocompatible UiO-66(Zr) MOF was used to study the adsorption and release conditions of ibuprofen, naproxen, and diclofenac using a theoretical and experimental approximation. DFT results showed that the MOF-drug interaction was due to an intermolecular hydrogen bond between protons of the groups in the defect sites, (μ - OH, and - OH) and a lone pair of oxygen carboxyl functional group of the NSAIDs. Also, the experimental results suggest that the solvent where the drug is dissolved affects the adsorption process. The adsorption kinetics are similar between the drugs, but the maximum load capacity differs for each drug. The release kinetics assay showed a solvent dependence kinetics whose maximum liberation capacity is affected by the interaction between the drug and the material. Finally, the biological assays show that none of the systems studied are cytotoxic for HMVEC. Additionally, the wound healing assay suggests that the UiO-66(Zr) material has potential application on the wound healing process. However, further studies should be done.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Metal-Organic Frameworks; Drug Liberation; Drug Delivery Systems; Naproxen; Ibuprofen; Humans; Adsorption; Drug Carriers; Diclofenac; Cell Survival; Phthalic Acids
PubMed: 38663750
DOI: 10.1016/j.jconrel.2024.04.035 -
Journal of Pharmaceutical Sciences Jul 2024Our study focuses on creating hybrid compounds and assessing their suitability for use in skincare products. The synergistic combination of Kojic acid, NSAIDs, and...
Our study focuses on creating hybrid compounds and assessing their suitability for use in skincare products. The synergistic combination of Kojic acid, NSAIDs, and Palmitic acid proved to be an effective approach in inhibiting melanin production, making it a promising solution for individuals with hyperpigmentation concerns with Kojic acid (KA) Ibuprofen monoester (IBUM) and Ibuprofen-Kojic acid-Palmitic acid diester (IBUD) exhibiting a potential tyrosinase (38 % and 49 % inhibition at 200 µM) and anti-melanogenesis activity (77 % and 79 % inhibition at 100 µM). Furthermore, these compounds exhibited potent anti-inflammatory effects, Kojic acid-Diclofenac monoester (DICM) and Diclofenac-Kojic acid-Palmitic acid diester (DICD) offering potential benefits for inflammation by lowering the paw volume. A stability study under chemical conditions and enzymatic conditions was also performed, wherein DICM and DICD showed a better half-life of 515, 593 h under chemical stability and 6.3, 7.5 h under enzymatic stability studies respectively. The diester hybrids IBUD, DICD, Naproxen-Kojic acid-Palmitic acid diester (NAPD) showed a better permeation and penetration profiles compared to their parent drugs. In-vitro cell line studies were conducted to assess the safety and efficacy of these hybrid esters, with promising results. The dual inhibitor demonstrated minimal cytotoxicity and remarkable anti-melanogenic and anti-inflammatory activities, showing its potential as a versatile agent in addressing both melanogenesis and inflammation.
Topics: Palmitic Acid; Melanins; Pyrones; Anti-Inflammatory Agents, Non-Steroidal; Animals; Monophenol Monooxygenase; Mice; Inflammation; Esters; Male; Rats; Humans; Ibuprofen; Diclofenac; Melanogenesis
PubMed: 38663499
DOI: 10.1016/j.xphs.2024.04.019 -
European Child & Adolescent Psychiatry May 2024
Topics: Methylphenidate; Humans; Central Nervous System Stimulants; World Health Organization; Drugs, Essential; Attention Deficit Disorder with Hyperactivity
PubMed: 38662057
DOI: 10.1007/s00787-024-02443-5 -
Environmental Toxicology and Chemistry Jun 2024Pharmaceuticals are found in aquatic environments due to their widespread use and environmental persistence. To date, a range of impairments to aquatic organisms has... (Comparative Study)
Comparative Study
Pharmaceuticals are found in aquatic environments due to their widespread use and environmental persistence. To date, a range of impairments to aquatic organisms has been reported with exposure to pharmaceuticals; however, further comparisons of their impacts across different species on the molecular level are needed. In the present study, the crustacean Daphnia magna and the freshwater fish Japanese medaka, common model organisms in aquatic toxicity, were exposed for 48 h to the common analgesics acetaminophen (ACT), diclofenac (DCF), and ibuprofen (IBU) at sublethal concentrations. A targeted metabolomic-based approach, using liquid chromatography-tandem mass spectrometry to quantify polar metabolites from individual daphnids and fish was used. Multivariate analyses and metabolite changes identified differences in the metabolite profile for D. magna and medaka, with more metabolic perturbations for D. magna. Pathway analyses uncovered disruptions to pathways associated with protein synthesis and amino acid metabolism with D. magna exposure to all three analgesics. In contrast, medaka exposure resulted in disrupted pathways with DCF only and not ACT and IBU. Overall, the observed perturbations in the biochemistry of both organisms were different and consistent with assessments using other endpoints reporting that D. magna is more sensitive to pollutants than medaka in short-term studies. Our findings demonstrate that molecular-level responses to analgesic exposure can reflect observations of other endpoints, such as immobilization and mortality. Thus, environmental metabolomics can be a valuable tool for selecting sentinel species for the biomonitoring of freshwater ecosystems while also uncovering mechanistic information. Environ Toxicol Chem 2024;43:1339-1351. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Topics: Animals; Oryzias; Daphnia; Acetaminophen; Ibuprofen; Water Pollutants, Chemical; Diclofenac; Metabolomics; Daphnia magna
PubMed: 38661510
DOI: 10.1002/etc.5876 -
Clinical Autonomic Research : Official... Apr 2024
Topics: Humans; Guanfacine; NAV1.7 Voltage-Gated Sodium Channel; Male; Primary Dysautonomias; Female; Adult; Middle Aged
PubMed: 38652422
DOI: 10.1007/s10286-024-01029-0 -
Journal of Agricultural and Food... May 2024This work seeks to generate new knowledge about the mechanisms underlying the protective effects of cranberry against urinary tract infections (UTI). Using Caco-2 cells...
This work seeks to generate new knowledge about the mechanisms underlying the protective effects of cranberry against urinary tract infections (UTI). Using Caco-2 cells grown in Transwell inserts as an intestinal barrier model, we found that a cranberry-derived digestive fluid (containing 135 ± 5 mg of phenolic compounds/L) increased transepithelial electrical resistance with respect to control (ΔTEER = 54.5 Ω cm) and decreased FITC-dextran paracellular transport by about 30%, which was related to the upregulation of the gene expression of tight junction (TJ) proteins (i.e., occludin, zonula occludens-1 [ZO-1], and claudin-2) (∼3-4-fold change with respect to control for claudin-2 and ∼2-3-fold for occludin and ZO-1). Similar protective effects, albeit to a lesser extent, were observed when Caco-2 cells were previously infected with uropathogenic (UPEC). In a urinary barrier model comprising T24 cells grown in Transwell inserts and either noninfected or UPEC-infected, treatments with the cranberry-derived phenolic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and phenylacetic acid (PAA) (250 μM) also promoted favorable changes in barrier integrity and permeability. In this line, incubation of noninfected T24 cells with these metabolites induced positive regulatory effects on claudin-2 and ZO-1 expression (∼3.5- and ∼2-fold change with respect to control for DOPAC and ∼1.5- and >2-fold change with respect to control for PAA, respectively). Overall, these results suggest that the protective action of cranberry polyphenols against UTI might involve molecular mechanisms related to the integrity and functionality of the urothelium and intestinal epithelium.
Topics: Vaccinium macrocarpon; Humans; Urinary Tract Infections; Polyphenols; Caco-2 Cells; Plant Extracts; Zonula Occludens-1 Protein; Uropathogenic Escherichia coli; Occludin; Intestinal Mucosa; Tight Junctions; Fruit; Intestines; Escherichia coli Infections
PubMed: 38651941
DOI: 10.1021/acs.jafc.3c07169 -
Organic & Biomolecular Chemistry May 2024A cost-effective, practical, straightforward and scalable synthesis of α-pyrones base- and sulfur-promoted annulation of phenylacetates and chalcones is reported....
A cost-effective, practical, straightforward and scalable synthesis of α-pyrones base- and sulfur-promoted annulation of phenylacetates and chalcones is reported. Generated from the starting components by using dbu as a base catalyst, the Michael adducts underwent a smooth oxidative cyclization into 3,4,6-triaryl-2-pyranones upon heating with DABCO and sulfur in DMSO. Extension to malonate in place of phenylacetates led to 4,6-diaryl-2-pyranone-2-carboxylates.
PubMed: 38651649
DOI: 10.1039/d4ob00479e