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1.
Molecules ; 29(20)2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39459220

RESUMO

Nickel manganese oxide (NiMnO3) combines magnetic and dielectric properties, making it a promising material for sensor and supercapacitor applications, as well as for catalytic water splitting. The efficiency of its utilization is notably influenced by particle size. In this study, we investigate the influence of thermal treatment parameters on the phase composition of products from alkali co-precipitation of nickel and manganese (II) ions and identify optimal conditions for synthesizing phase-pure nickel manganese oxide. Ultrafine nanoparticles of NiMnO3 (with sizes as small as 2 nm) are obtained via liquid-phase ultrasonic dispersion, exhibiting a narrow size distribution. A systematic exploration of the solvent nature (water, N-methyl-2-pyrrolidone, dimethyl sulfoxide, dimethylformamide) on the efficiency of ultrasonic dispersion of NiMnO3 nanoparticles is provided. It is demonstrated that particle size is influenced not only by absorbed acoustic power, dependent on the physical properties of the used solvent (boiling temperature, gas solubility, viscosity, density) but also by the chemical stability of the solvent under prolonged ultrasonic treatment. Our findings provide insights for designing ultrasonic treatment protocols for nanoparticle dispersions with tailored particle sizes.

2.
Anal Chim Acta ; 1329: 343222, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39396287

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is emerging as a promising cancer treatment. The PDT efficacy is primarily attributed to the generation of singlet oxygen (1O2), stemming from the integrated effects of the photosensitizer, oxygen, and light. The singlet oxygen quantum yield (ΦΔ) serves as a bridge that links these parameters to the overall efficacy of PDT. The near-infrared luminescence of 1O2 provides a direct way for determining ΦΔ, but suffers from a poor signal-to-noise ratio. While the chemical trap probe method is detection-friendly, but it has a strict requirement for the excitation wavelength. Therefore, the existing methods for ΦΔ measurement are insufficient. RESULTS: In this work, we developed an approach to determine ΦΔ of a broader range of photosensitizers using only the commonly used solvent dimethyl sulfoxide (DMSO), which can be oxidized by 1O2 to dimethyl sulfone. This method establishes the relationship between 1O2 production and changes in DMSO absorption spectra, eliminating the need for additional chemical probes. This method was validated by measuring the ΦΔ of rose bengal (RB) through systematic changes in absorption spectrum of DMSO under various RB concentrations and different excitation light power densities. Moreover, the ΦΔ of hematoporphyrin monomethyl ether (HMME), as determined by this method, is consistent with measurements obtained using the 1,3-diphenylisobenzofuran (DPBF) trapping probe. This consistency further validates the reliability of this method. SIGNIFICANCE AND NOVELTY: This work presents a direct, probe-free method to determine ΦΔ, reducing potential interference and expanding the range of useable excitation wavelengths. Its ability to measure ΦΔ using only DMSO enhances the accuracy of photosensitizer measurement, and broadens the applicability of the method to a wide range of samples, thereby advancing research on the properties of photosensitizers and further promoting the development of PDT.

3.
Arch Dermatol Res ; 316(10): 687, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39400574

RESUMO

BACKGROUND: Macular amyloidosis (MA) could be of cosmetic concern with a significant psychological impact for patients, and its treatment is challenging. AIM OF THE WORK: To compare the efficacy and safety of combined fractional CO2 laser with dimethyl sulfoxide (DMSO) 50% versus fractional CO2 laser alone in the treatment of macular amyloidosis. PATIENTS AND METHODS: Twenty patients with macular amyloidosis were treated with monthly session of fractional CO2 laser only in one side of the lesion (area A), and fractional laser followed by application of DMSO 50% solution in the other side of the lesion (area B). All patients were evaluated clinically, by dermoscope and histopathology before and 3 months after the end of 4 treatment sessions. RESULTS: Both treatments showed significant decrease of pigmentation after treatment (p < 0.001). There was non-significant decrease in rippling on both sides (p = 0.06). The median itching score dropped significantly after treatment from 9 to 3.5 in area A (laser only) and to 2 in area B (laser and DMSO), with non-significant difference between both areas (P = 0.244). Dermoscopic features after treatment showed fading and decreasing in multiple features in both areas A and B, with non-significant difference between the 2 areas. Histopathologically, there was significant reduction in the amyloid deposition after treatment in both areas A and B without significant difference between both areas. CONCLUSION: both fractional CO2 laser combined with topical DMSO 50% and fractional CO2 laser alone are safe and effective treatment options for MA with significant clinical improvement.


Assuntos
Amiloidose , Dimetil Sulfóxido , Lasers de Gás , Humanos , Lasers de Gás/uso terapêutico , Dimetil Sulfóxido/administração & dosagem , Dimetil Sulfóxido/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Amiloidose/diagnóstico , Amiloidose/terapia , Amiloidose/patologia , Terapia Combinada/métodos , Adulto
4.
Toxicol Lett ; 401: 82-88, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303962

RESUMO

Hydrogen sulfide (H2S) is a toxic gas emitted through natural and anthropogenic activities. Chronic exposure to inhaled H2S at low sub-toxic levels is common among workers in oil refineries and may have important health implications. Inhaled H2S can be oxidized to thiosulfate or methylated to dimethylsulfide (DMS) which can be methylated to the novel human metabolite trimethylsulfonium (TMS) or oxidized to dimethylsulfoxide (DMSO) but the extent of methylation of inhaled H2S is currently unknown in humans. A total of 80 participants were recruited of which 40 were workers in an oil refinery in Kurdistan region, Iraq including those working in close contact with the facility area where H2S was measured at 1.5-5.0 mg m-3, and 40 controls living in a nearby city with no detectable H2S or perceptible odor (<0.1 mg m-3). A total of 240 urine samples were measured for multiple H2S-related metabolites. DMSO was consistently found in all urine samples with concentrations generally within the range of 1.0-10 µM. Although these concentrations were 10-100-fold higher than TMS urinary levels, clear correlation between DMSO and TMS was observed (rs 0.55, P < 0.0001), which supports DMS as common precursor. DMSO urinary levels were elevated in the oil refinery workers in close contact with the facilities (5.0 vs. 3.3 µM, P 0.03), but TMS was unaltered (0.13 vs. 0.14 µM, P 0.68). Overall, the results suggest that the investigated methylation metabolites are not sufficiently sensitive to low occupational exposure levels of inhaled H2S.

5.
Molecules ; 29(16)2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39203050

RESUMO

In the first part of this study, the electrochemical polymerization of two compounds, 3,5-dihydroxybenzoic acid and 2',6'-dihydroxyacetophenone, was compared in dimethyl sulfoxide solvent on platinum and glassy carbon electrodes. The voltammograms obtained showed remarkable differences between the two monomers and between the two electrode materials. The acetophenone derivative formed electropolymer remnants at the electrodes, while in the case of the benzoic acid derivative, practically no passivation occurred, and the scanning electron microscopic results reinforced this. A few stackings adsorbed only after electropolymerization from a highly concentrated solution of dihydroxybenzoic acid. As a modifying layer on the platinum and glassy carbon electrodes, the prepared films from 2',6'-dihydroxyacetophenone were tested for tributylamine in acetonitrile and in an aqueous solution of a redox-active compound, hydroquinone, during the stirring of the solution. More stable amperometric current signals could be reached with modified platinum than with glassy carbon, and the significant influence of the organic washing liquid after deposition was established via the study of noise level. In this respect, acetone was the best choice. The amperometric signals with the modified platinum obtained upon the addition of aliquots of the stock solution resulted in a 3.29 µM detection limit.

6.
J Neurosci Methods ; 411: 110255, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39159871

RESUMO

Dimethyl sulfoxide (DMSO) is commonly used to dissolve water-insoluble drugs due to its dipolar and aprotic properties. It also serves as a vehicle in many pharmacological studies. However, it has been reported that DMSO can induce seizures in human patients, lower seizure threshold in vivo, and modulate ion receptors activities in vitro. Therefore, we investigated here the effect of 0.03 % and 0.06 % DMSO, which are 10-50 times lower than what usually employed in previous studies, in the 4-aminopyridine (4AP) model of epileptiform synchronization in male mouse brain slices. We found that 0.03 % and 0.06 % DMSO increase 4AP-induced ictal discharge rate, while 0.06 % DMSO decreases ictal discharge duration. Our results suggest that the effects of DMSO on neuronal excitability deserve further analysis and that investigators need to be aware of its confounding effect as a solvent, even at very low concentrations.


Assuntos
4-Aminopiridina , Dimetil Sulfóxido , Animais , 4-Aminopiridina/farmacologia , Dimetil Sulfóxido/farmacologia , Masculino , Camundongos , Epilepsia/fisiopatologia , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Bloqueadores dos Canais de Potássio/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia
7.
Environ Pollut ; 360: 124653, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39095002

RESUMO

Protozoa play a pivotal role in the microbial cycle, and ciliated protozoan grazing habits are associated with dimethyl sulfide (DMS) cycle. Many studies have explored the impacts of nanoplastics (NPs) and microplastics (MPs) on ecotoxicological effects of ciliates. However, limited research exists on NPs and MPs influences on the production of organic sulfur compounds. The impact of NPs and MPs on the production of dimethyl sulfoxide (DMSO) and carbonyl sulfide (COS) remains unclear. Therefore, we examined the impacts of three concentrations (1 × 105, 5 × 105, and 1 × 106 items/mL) of polystyrene (PS) NPs (50 nm) and MPs (1 and 5 µm) on the ecotoxicology and DMS/dimethylsulfoniopropionate (DMSP)/DMSO/COS production in the ciliate Uronema marinum. NPs and MPs exposure were found to reduce the abundance, growth rate, volume, and biomass of U. marinum. Additionally, NPs and MPs increased the superoxide anion radical (O2˙─) production rates and malondialdehyde (MDA) contents (24 h), leading to a decline in glutathione (GSH) content and an ascend in superoxide dismutase (SOD) activity to mitigate the effects of reactive oxygen species (ROS). Exposure to PS NPs and MPs decreased the ingestion rates of algae by 7.5-14.4%, resulting in decreases in DMS production by 56.8-85.4%, with no significant impact on DMSO production. The results suggest a distinct pathway for the production of DMSO or COS compared to DMS. These findings help us to understand the NPs and MPs impacts on the marine ecosystem and organic sulfur compound yield, potentially influencing the global climate.


Assuntos
Antioxidantes , Cilióforos , Microplásticos , Cilióforos/fisiologia , Antioxidantes/metabolismo , Microplásticos/toxicidade , Poluentes Químicos da Água , Nanopartículas/toxicidade , Sulfetos/toxicidade
8.
Lab Invest ; 104(9): 102125, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39168250

RESUMO

Lymph node status is a key factor in determining stage, treatment, and prognosis in cancers. Small lymph nodes in fat-rich gastrointestinal and breast cancer specimens are easily missed in conventional sampling methods. This study examined the effectiveness of the degreasing pretreatment with dimethyl sulfoxide (DMSO) in lymph node detection and its impact on the analysis of clinical treatment-related proteins and molecules. Thirty-three cases of gastrointestinal cancer specimens from radical gastrectomy and 63 cases of breast cancer specimens from modified radical mastectomy were included. After routine sampling of lymph nodes, the specimens were immersed in DMSO for 30 minutes for defatting. We assessed changes in the number of detected lymph nodes and pN staging in 33 gastrointestinal cancer specimens and 37 breast cancer specimens. In addition, we analyzed histologic characteristics, Masson trichrome special staining, and immunohistochemistry (gastrointestinal cancer: MMR, HER2, and PD-L1; breast cancer: ER, PR, AR, HER2, Ki-67, and PD-L1). Molecular status was evaluated for colorectal cancer (KRAS, NRAS, BRAF, and microsatellite instability) and breast cancer (HER2) in gastrointestinal cancer specimens and the remaining 26 breast cancer specimens. Compared with conventional sampling, DMSO pretreatment increased the detection rate of small lymph nodes (gastrointestinal cancer: P < .001; breast cancer: P < .001) and improved pN staging in 1 case each of gastric cancer, colon cancer, and rectal cancer (3/33; 9.1%). No significant difference in the morphology, special staining, protein, and molecular status of cancer tissue after DMSO treatment was found. Based on these results and our institutional experience, we recommend incorporating DMSO degreasing pretreatment into clinical pathologic sampling practices.


Assuntos
Neoplasias da Mama , Dimetil Sulfóxido , Neoplasias Gastrointestinais , Imuno-Histoquímica , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/tratamento farmacológico , Dimetil Sulfóxido/farmacologia , Idoso , Adulto , Masculino , Linfonodos/patologia , Linfonodos/metabolismo , Manejo de Espécimes/métodos , Metástase Linfática , Idoso de 80 Anos ou mais
9.
Front Bioeng Biotechnol ; 12: 1443795, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139293

RESUMO

Human induced pluripotent stem cells (hiPSCs) are an attractive cell source for regenerative medicine. For its widespread use as a starting material, a robust storage and distribution system in the frozen state is necessary. For this system, managing transient warming during storage and transport is essential, but how transient warming affects cells and the mechanisms involved are not yet fully understood. This study examined the influence of temperature cyclings (from -80°C to -150°C) on cryopreserved hiPSCs using a custom-made cryo Raman microscope, flow cytometry, and performance indices to assess viability. Raman spectroscopy indicated the disappearance of mitochondrial cytochrome signals after thawing. A reduction in the mitochondrial membrane potential was detected using flow cytometry. The performance indices indicated a decrease in attachment efficiency with an increase in the number of temperature cycles. This decrease was observed in the temperature cycle range above the glass transition temperature of the cryoprotectant. Raman observations captured an increase in the signal intensity of intracellular dimethyl sulfoxide (DMSO) during temperature cycles. Based on these results, we proposed a schematic illustration for cellular responses to temperature fluctuations, suggesting that temperature fluctuations above the glass-transition temperature trigger the movement of DMSO, leading to cytochrome c oxidation, mitochondrial damage, and caspase-mediated cell death. This enhances our understanding of the key events during cryopreservation and informs the development of quality control strategies for hiPSC storage and transport.

10.
Contact (Thousand Oaks) ; 7: 25152564231223480, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39108634

RESUMO

In this News and Views, I discuss our recent publication that established how steroidogenic acute regulatory-related lipid transfer domain-3 (STARD3), a membrane contact protein situated at lysosomal membranes, plays a role in the detoxification of cholesterol hydroperoxide. STARD3's methionine residues can be oxidized to methionine sulfoxide by cholesterol hydroperoxide, after which methionine sulfoxide reductases reduce the methionine sulfoxide residues back to methionine. The reaction also results in the reduction of the cholesterol hydroperoxide to an alcohol. The cyclic oxidation and reduction of methionine residues in STARD3 at membrane contact sites creates a catalytically efficient mechanism for detoxification of cholesterol hydroperoxide during cholesterol transport, thus protecting membrane contact sites and the entire cell against the toxicity of cholesterol hydroperoxide.

11.
Beilstein J Org Chem ; 20: 2108-2113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39189003

RESUMO

Access to original ortho thioether derivatives was achieved through a [3,3]-rearrangement in a one-pot two-step protocol. Several aryl-SCF3 compounds are reported by variation of the nitrile or of the trifluoroalkyl sulfoxide starting material. The variation of the perfluoroalkyl chain was also possible.

12.
J Agric Food Chem ; 72(34): 19040-19050, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39159198

RESUMO

In the brewing process, methionine is a decisive amino acid for (off-)flavor formation. A significant part of methionine is oxidized to methionine sulfoxide (MetSO) in malt. We hypothesized that MetSO and MetSO2 are metabolized to volatile compounds during yeast fermentation and examined whether the yeast Saccharomyces cerevisiae is able to catabolize l-MetSO and l-MetSO2 in free and dipeptide-bound forms. We also investigated the stability of l-methionine sulfoximine and S-methylmethionine. Cell viability in the presence of the test compounds was at least 90%. Both free and peptide-bound test substances were metabolized by Saccharomyces cerevisiae. l-MetSO was degraded most rapidly as the free amino acid, while l-MetSO2 was degraded most rapidly bound in dipeptides. We observed a different degradation behavior of the (R) and (S) diastereoisomers for l-MetSO and l-methionine sulfoximine. Furthermore, we detected methionol as the only metabolite of MetSO. Methionol sulfoxide was not formed. MetSO2 was not converted to methionol or methionol sulfone but to the respective α-hydroxy acid. We conclude that the reduction of MetSO to methionine proceeds faster than transamination. The occurrence of MetSO or MetSO2 in brewing malt will not lead to the formation of hitherto unknown volatile metabolites of the Ehrlich pathway.


Assuntos
Fermentação , Metionina , Oxirredução , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/química , Metionina/metabolismo , Metionina/química , Metionina/análogos & derivados , Peptídeos/metabolismo , Peptídeos/química , Modelos Biológicos
13.
Structure ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39216472

RESUMO

Non-heme iron-dependent sulfoxide/selenoxide synthases (NHISS) constitute a unique metalloenzyme class capable of installing a C-S/Se bond onto histidine to generate thio/selenoimidazole antioxidants, such as ergothioneine and ovothiol. These natural products are increasingly recognized for their health benefits. Among associated ergothioneine-biosynthetic enzymes, type IV EgtBs stand out, as they exhibit low sequence similarity with other EgtB subfamilies due to their recent divergence from the ovothiol-biosynthetic enzyme OvoA. Herein, we present crystal structures of two representative EgtB-IV enzymes, offering insights into the basis for this evolutionary convergence and enhancing our understanding of NHISS active site organization more broadly. The ability to interpret how key residues modulate substrate specificity and regioselectivity has implications for downstream identification of divergent reactivity within the NHISS family. To this end, we identify a previously unclassified clade of OvoA-like enzymes with a seemingly hybrid set of characteristics, suggesting they may represent an evolutionary intermediate between OvoA and EgtB-IV.

14.
Chemistry ; : e202402875, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148303

RESUMO

Highly enantioselective Rh-catalyzed allylic substitution of the racemic branched allylic substrates with 2-fluoromalonate was realized enabled by a novel chiral sulfoxide-imine-olefin ligand under mild reaction conditions. The utilization of CuSO4 is beneficial for improving the enantioselectivity. Notably, the chiral fluoro-containing allyl products can be employed in a selective cyclic esterification to form chiral α-fluorolactone bearing vicinal stereogenic centers.

15.
Biomed Phys Eng Express ; 10(5)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38955138

RESUMO

This work aims to improve the post stabilty of reusable potassium iodide hydrogel dosimter. A reusable and low-cost radiochromic dosimeter containing a gel matrix of polyvinyl alcohol, potassium iodide dye, froctose as reducing agent and glutaraldehyde as cross-linking agent was developed for dose calibration in radiotherapy. The gel samples were exposed to different absorbed doses using a medical linear acceleration. UV-vis Spectrophotometry was utilized to investigate the changes in optical-properties of irradiated gels with regard to peak wavelength of 353 nm. The stability of the gel (one of the most limitation of using this dosimeter) was improved significantly by the addition of certain concentrations of dimethyl sulfoxide. The two-dimensional optical imaging system of charge-coupled-device (CCD) camera with a uniform RGB light-emitting-diode (LED) array source was used for diffusion coefficient purpose using two dimensional gel template. The value of diffusion coefficient reported is significant and highly reduced compared with other dosimeters reported in the literatures. Moreover, heating the improved gels to certain temperatures results in resetting their optical properties, which makes it possible to reuse for multiple times.


Assuntos
Estudos de Viabilidade , Álcool de Polivinil , Iodeto de Potássio , Dosímetros de Radiação , Álcool de Polivinil/química , Iodeto de Potássio/química , Calibragem , Géis/química , Humanos , Hidrogéis/química , Radiometria/métodos , Radiometria/instrumentação , Dimetil Sulfóxido/química , Glutaral/química , Difusão , Temperatura
16.
Sci Rep ; 14(1): 16937, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043853

RESUMO

In this research project, a versatile procedure has been designed for the preparation of supported copper@curcumin on magnetic graphene oxide nanoparticles (GO@Fe3O4@Cur-Cu). The structure of prepared nanocatalyst was characterized by several techniques including; Fourier transform infrared, powder X-ray diffraction, thermal gravimetric analysis, energy dispersive X-ray analysis, inductively coupled plasma optical emission spectroscopy, vibrating sample magnetometer, transmission electron microscopy, and scanning electron microscopy analyses. The catalytic properties of GO@Fe3O4@Cur-Cu were examined for the efficient synthesis of polyhydroquinolines as well as the preparation of sulfoxides through selective oxidation of sulfides in the presence of hydrogen peroxide.

17.
Cell Mol Life Sci ; 81(1): 306, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023560

RESUMO

Recent advances in stem cell research have led to the creation of organoids, miniature replicas of human organs, offering innovative avenues for studying diseases. Kidney organoids, with their ability to replicate complex renal structures, provide a novel platform for investigating kidney diseases and assessing drug efficacy, albeit hindered by labor-intensive generation and batch variations, highlighting the need for tailored cryopreservation methods to enable widespread utilization. Here, we evaluated cryopreservation strategies for kidney organoids by contrasting slow-freezing and vitrification methods. 118 kidney organoids were categorized into five conditions. Control organoids followed standard culture, while two slow-freezing groups used 10% DMSO (SF1) or commercial freezing media (SF2). Vitrification involved V1 (20% DMSO, 20% Ethylene Glycol with sucrose) and V2 (15% DMSO, 15% Ethylene Glycol). Assessment of viability, functionality, and structural integrity post-thawing revealed notable differences. Vitrification, particularly V1, exhibited superior viability (91% for V1, 26% for V2, 79% for SF1, and 83% for SF2 compared to 99.4% in controls). 3D imaging highlighted distinct nephron segments among groups, emphasizing V1's efficacy in preserving both podocytes and tubules in kidney organoids. Cisplatin-induced injury revealed a significant reduction in regenerative capacities in organoids cryopreserved by flow-freezing methods, while the V1 method did not show statistical significance compared to the unfrozen controls. This study underscores vitrification, especially with high concentrations of cryoprotectants, as an effective approach for maintaining kidney organoid viability and structure during cryopreservation, offering practical approaches for kidney organoid research.


Assuntos
Criopreservação , Crioprotetores , Rim , Organoides , Criopreservação/métodos , Organoides/citologia , Organoides/efeitos dos fármacos , Organoides/metabolismo , Humanos , Rim/citologia , Crioprotetores/farmacologia , Vitrificação , Dimetil Sulfóxido/farmacologia , Etilenoglicol/farmacologia , Congelamento , Sobrevivência Celular/efeitos dos fármacos
18.
J Toxicol Environ Health A ; 87(20): 811-823, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-38967335

RESUMO

During the key event 1 of skin sensitization defined as covalent binding or haptenization of sensitizer to either thiol or amino group of skin proteins, a sensitizer not only covalently binds with skin proteins but also interacts with nucleophilic small molecules such as glutathione (GSH). Although GSH would not be directly associated with skin sensitization, this interaction may be applied for developing an alternative test method simulating key event 1, haptenization. Thus, the aim of the present study was to examine whether N-acetyl-L-cysteine methyl ester (NACME), a thiol-containing compound, was selected as an electron donor to determine whether NACME reacted with sensitizers. Following a reaction of NACME with a sensitizer in a 96-well plate, the remaining NACME was measured spectrophotometrically using 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Following the optimization of test conditions with two different vehicles, such as acetonitrile (ACN) and dimethyl sulfoxide (DMSO), 64 test chemicals were tested to determine the predictive capacity of current NACME test method. The results obtained showed, the predictive capacity of 94.6% sensitivity, 88.9% specificity, and 92.2% accuracy utilizing DMSO as a vehicle with a cutoff NACME depletion of 5.85%. The three parameters were also over 85% in case of ACN. These values were comparable to or better than other OECD-approved test methods. Data demonstrated that a simple thiol-containing compound NACME might constitute as a reliable candidate for identifying reactive skin sensitizers, and that this method be considered as practical method as a screening tool for assessing a chemical's tendency to initiate skin sensitization.


Assuntos
Acetilcisteína , Acetilcisteína/análogos & derivados , Espectrofotometria , Humanos , Pele/efeitos dos fármacos , Ácido Ditionitrobenzoico/química , Haptenos/toxicidade , Haptenos/química , Alternativas aos Testes com Animais/métodos , Animais
19.
Biomedicines ; 12(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38927463

RESUMO

Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed if zinc iodide (ZnI) supplementation through dimethyl sulfoxide (DMSO) modifies the action of MMPs in isolated human lung fibroblasts. The expression and activity of two gelatinases, MMP-2 and MMP-9, were determined by gelatin zymography and enzyme-linked immuno-sorbent assay (ELISA). Collagen degradation was determined by cell-based ELISAs. Collagen type I and fibronectin deposition was stimulated by human recombinant tumor growth factor ß1 (TGF-ß1). Untreated fibroblasts secreted MMP-2 but only minute amounts of MMP-9. TGF-ß1 (5 ng/mL) reduced MMP-2 secretion, but stimulated collagen type I and fibronectin deposition. All the effects of TGF-ß1 were significantly reduced in cells treated with ZnI-DMSO over 24 h, while ZnI and DMSO alone had a lower reducing effect. ZnI-DMSO alone did not increase MMP secretion but enhanced the ratio of active to inactive of MMP-2. ZnI alone had a lower enhancing effect than ZnI-DMSO on MMP activity. Furthermore, MMP-2 activity was increased by ZnI-DMSO and ZnI in the absence of cells. Soluble collagen type I increased in the medium of ZnI-DMSO- and ZnI-treated cells. Blocking MMP activity counteracted all the effects of ZnI-DMSO. Conclusion: The data suggest that the combination of ZnI with DMSO reduces fibrotic processes by increasing the degradation of collagen type I by up-regulating the activity of gelatinases. Thus, the combination of ZnI with DMSO might be considered for treatment of fibrotic disorders of the lung. DMSO supported the beneficial effects of ZnI.

20.
Int J Mol Sci ; 25(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38928132

RESUMO

Ruthenium chloride (RuCl3) is widely utilized for synthesis and catalysis of numerous compounds in academia and industry and is utilized as a key molecule in a variety of compounds with medical applications. Interestingly, RuCl3 has been demonstrated to modulate human plasmatic coagulation and serves as a constituent of a compounded inorganic antivenom that neutralizes the coagulopathic effects of snake venom in vitro and in vivo. Using thrombelastography, this investigation sought to determine if RuCl3 inhibition of the fibrinogenolytic effects of Crotalus atrox venom could be modulated by vehicle composition in human plasma. Venom was exposed to RuCl3 in 0.9% NaCl, phosphate-buffered saline (PBS), or 0.9% NaCl containing 1% dimethyl sulfoxide (DMSO). RuCl3 inhibited venom-mediated delay in the onset of thrombus formation, decreased clot growth velocity, and decreased clot strength. PBS and DMSO enhanced the effects of RuCl3. It is concluded that while a Ru-based cation is responsible for significant inhibition of venom activity, a combination of Ru-based ions containing phosphate and DMSO enhances RuCl3-mediated venom inhibition. Additional investigation is indicated to determine what specific Ru-containing molecules cause venom inhibition and what other combinations of inorganic/organic compounds may enhance the antivenom effects of RuCl3.


Assuntos
Antivenenos , Coagulação Sanguínea , Venenos de Crotalídeos , Crotalus , Dimetil Sulfóxido , Humanos , Dimetil Sulfóxido/farmacologia , Dimetil Sulfóxido/química , Antivenenos/farmacologia , Antivenenos/química , Venenos de Crotalídeos/antagonistas & inibidores , Venenos de Crotalídeos/farmacologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Compostos de Rutênio/farmacologia , Compostos de Rutênio/química , Cloreto de Sódio/farmacologia , Cloreto de Sódio/química , Tromboelastografia , Serpentes Peçonhentas
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