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Introduction: Any disruption in renal function can have cascading effects on overall health. Understanding how a heat-born toxicant like acrylamide (ACR) affects kidney tissue is vital for realizing its broader implications for systemic health. Methods: This study investigated the ACR-induced renal damage mechanisms, particularly focusing on the regulating role of miR-21a-5p/fibrotic and miR-122-5p/inflammatory signaling pathways via targeting Timp-3 and TP53 proteins in an In silico preliminary study. Besides, renal function assessment, oxidative status, protein profile, and the expression of renal biomarkers (Timp-1, Keap-1, Kim-1, P53, TNF-α, Bax, and Caspase3) were assessed in a 60-day experiment. The examination was additionally extended to explore the potential protective effects of green-synthesized zinc oxide nanoparticles (ZNO-MONPs). A four-group experiment including control, ZNO-MONPs (10 mg/kg b.wt.), ACR (20 mg/kg b.wt.), and ZNO-MONPs + ACR was established encompassing biochemical, histological, and molecular levels. The study further investigated the protein-binding ability of ZNO and MONPs to inactivate caspase-3, Keap-1, Kim-1, and TNFRS-1A. Results: ZNO-MONPs significantly reduced ACR-induced renal tissue damage as evidenced by increased serum creatinine, uric acid, albumin, and oxidative stress markers. ACR-induced oxidative stress, apoptosis, and inflammationare revealed by biochemical tests, gene expression, and the presence of apoptotic nuclei microscopically. Also, molecular docking revealed binding affinity between ACR-BCL-2 and glutathione-synthetase, elucidating the potential mechanisms through which ACR induces renal damage. Notably, ZNO-MONPs revealed a protective potential against ACR-induced damage. Zn levels in the renal tissues of ACR-exposed rats were significantly restored in those treated with ACR + ZNO-MONPs. In conclusion, this study establishes the efficacy of ZNO-MONPs in mitigating ACR-induced disturbances in renal tissue functions, oxidative stress, inflammation, and apoptosis. The findings shed light on the potential renoprotective activity of green-synthesized nanomaterials, offering insights into novel therapeutic approaches for countering ACR-induced renal damage.
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Atomoxetine is a psychostimulant drug used for the treatment of attention-deficit/hyperactivity disorder (ADHD) symptoms in people with autism. Herein, eco-friendly fluorescent carbon quantum dots (CQDs) were synthesized using black-eyed pea beans and characterized for the purpose of quantifying atomoxetine in pharmaceutical capsules and human plasma. The selectivity of these CQDs towards atomoxetine was improved by functionalizing their surface with an atomoxetine-tetraphenylborate ion complex. The quantification of atomoxetine is based on measuring the fluorescence quenching of the functionalized CQDs in response to varying concentrations of atomoxetine. The Stern-Volmer plot was employed to investigate the mechanism through which atomoxetine quenches the fluorescence intensity of the CQDs. The outcomes indicated a dynamic quenching mechanism. The applied method was optimized and validated in compliance with ICH requirements, resulting in excellent linearity across the concentration range of 50-800 ng/mL. The developed method was successfully used to quantify atomoxetine in pharmaceutical dosage form and human plasma with acceptable accuracy and precision outcomes. In addition, the method was applied for clinical pharmacokinetic study of atomoxetine in the plasma of children diagnosed with both autism and ADHD. Atomoxetine was rapidly absorbed after a single oral dose of 10 mg, reaching maximum concentration within two hours and having a half-life (t1/2) of 3.11 h. Moreover, the method demonstrates a notable degree of eco-friendliness, as evidenced by two greenness evaluation metrics; Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE).
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Cloridrato de Atomoxetina , Corantes Fluorescentes , Pontos Quânticos , Espectrometria de Fluorescência , Cloridrato de Atomoxetina/farmacocinética , Cloridrato de Atomoxetina/sangue , Humanos , Pontos Quânticos/química , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Espectrometria de Fluorescência/métodos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Criança , Masculino , Transtorno Autístico/tratamento farmacológico , Reprodutibilidade dos Testes , Limite de DetecçãoRESUMO
The vast dissemination of resistance to different antibiotics among bacterial pathogens, especially foodborne pathogens, has drawn major research attention. Thus, many attempts have been made to reveal novel alternatives to the current antibiotics. Due to their variable pharmacologically active phytochemicals, plants represent a good solution for this issue. This study investigated the antibacterial potential of Kumquat or Fortunella japonica methanol extract (FJME) against Salmonella typhimurium clinical isolates. Gas chromatography coupled with mass spectrometry (GC/MS) characterized 39 compounds in FJME. Palmitic acid (15.386%) and cis-vaccenic acid (15.012%) are the major active constituents detected by GC/MS. Remarkably, FJME had minimum inhibitory concentrations from 128 to 512 µg/mL in vitro. In addition, a systemic infection model revealed the in vivo antibacterial action of FJME. The antibacterial therapeutic activity of FJME was noticed by improving the histological features of the liver and spleen. Moreover, there was a perceptible lessening (p < 0.05) of the levels of the oxidative stress markers (nitric oxide and malondialdehyde) using ELISA. In addition, the gene expression of the proinflammatory cytokine (interleukin 6) was downregulated. On the other hand, there was an upregulation of the anti-inflammatory cytokine (interleukin 10). Accordingly, future clinical investigations should be done to reveal the potential antibacterial action of FJME on other food pathogens.
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Antibacterianos , Frutas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Salmonella typhimurium , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Salmonella typhimurium/efeitos dos fármacos , Antibacterianos/farmacologia , Frutas/microbiologia , Frutas/química , Animais , Camundongos , Infecções por Salmonella/microbiologia , Infecções por Salmonella/tratamento farmacológicoRESUMO
Exposure to acrylic amide (AD) has garnered worldwide attention due to its potential adverse health effects, prompting calls from the World Health Organization for intensified research into associated risks. Despite this, the relationship between oral acrylic amide (acrylamide) (AD) exposure and pulmonary dysfunction remains poorly understood. Our study aimed to investigate the correlation between internal oral exposure to AD and the decline in lung function, while exploring potential mediating factors such as tissue inflammation, oxidative stress, pyroptosis, and apoptosis. Additionally, we aimed to evaluate the potential protective effect of zinc oxide nanoparticles green-synthesized moringa extract (ZNO-MONPs) (10â¯mg/kg b.wt) against ACR toxicity and conducted comprehensive miRNA expression profiling to uncover novel targets and mechanisms of AD toxicity (miRNA 223-3â¯P and miRNA 325-3â¯P). Furthermore, we employed computational techniques to predict the interactions between acrylic amide and/or MO-extract components and tissue proteins. Using a rat model, we exposed animals to oral acrylamide (20â¯mg/kg b.wt for 2 months). Our findings revealed that AD significantly downregulated the expression of miRNA 223-3â¯P and miRNA 325-3â¯P, targeting NLRP-3 & GSDMD, respectively, indicating the induction of pyroptosis in pulmonary tissue via an inflammasome activating pathway. Moreover, AD exposure resulted in lipid peroxidative damage and reduced levels of GPX, CAT, GSH, and GSSG. Notably, AD exposure upregulated apoptotic, pyroptotic, and inflammatory genes, accompanied by histopathological damage in lung tissue. Immunohistochemical and immunofluorescence techniques detected elevated levels of indicative harmful proteins including vimentin and 4HNE. Conversely, concurrent administration of ZNO-MONPs with AD significantly elevated the expression of miRNA 223-3â¯P and miRNA 325-3â¯P, protecting against oxidative stress, apoptosis, pyroptosis, inflammation, and fibrosis in rat lungs. In conclusion, our study highlights the efficacy of ZNO-MONPs NPs in protecting pulmonary tissue against the detrimental impacts of foodborne toxin AD.
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Inflamassomos , MicroRNAs , Extratos Vegetais , Piroptose , Ratos Sprague-Dawley , Transdução de Sinais , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Ratos , Masculino , Piroptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acrilamida/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Acrilamidas/toxicidade , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismoRESUMO
Futibatinib is a powerful inhibitor of fibroblast growth factor receptors that impedes its phosphorylation and subsequently leading to a reduction in in cell viability across various cell lines. Futibatinib was approved for initial use as an effective treatment for several diseases, including non-small cell lung cancer and breast cancer. Herein, a novel selective fluorescence probe was created for futibatinib quantification in various matrices, including pharmaceutical formulation and human plasma. The technique primarily depends on futibatinib's chemical conversion into a fluorescent product through a reaction with trimethylamine and bromoacetyl bromide. The created fluorescent probe exhibits maximum emission peak at 338 nm upon excitation at 248 nm. The method provided a low detection limit of 0.120 ng/mL and maintained a linear concentration-dependent relationship across the range of 1-200 ng/mL. High sensitivity, accuracy and precision were demonstrated for futibatinib quantification in pharmaceutical formulation and spiked plasma matrix by the method, which was validated in accordance with ICH requirements.
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Limite de Detecção , Espectrometria de Fluorescência , Humanos , Espectrometria de Fluorescência/métodos , Reprodutibilidade dos Testes , Corantes Fluorescentes/químicaRESUMO
Celecoxib and tramadol have been combined in a novel FDA-approved medication to address acute pain disorders requiring opioid treatment when other analgesics proved either intolerable or ineffective. The absorbance spectra of celecoxib and tramadol exhibit significant overlap, posing challenges for their individual quantification. This study introduces a spectrophotometric quantification approach for celecoxib and tramadol using a principle component regression assistive model to assist resolving the overlapped spectra and quantifying both drugs in their binary mixture. The model was constructed by establishing calibration and validation sets for the celecoxib and tramadol mixture, employing a five-level, two-factor experimental design, resulting in 25 samples. Spectral data from these mixtures were measured and preprocessed to eliminate noise in the 200-210 nm range and zero absorbance values in the 290-400 nm range. Consequently, the dataset was streamlined to 81 variables. The predicted concentrations were compared with the known concentrations of celecoxib and tramadol, and the errors in the predictions were evidenced calculating root mean square error of cross-validation and root mean square error of prediction. Validation results demonstrate the efficacy of the models in predicting outcomes; recovery rates approaching 100 % are demonstrated with relative root mean square error of prediction (RRMSEP) values of 0.052 and 0.164 for tramadol and celecoxib, respectively. The selectivity was further evaluated by quantifying celecoxib and tramadol in the presence of potentially interfering drugs. The model demonstrated success in quantifying celecoxib and tramadol in laboratory-prepared tablets, producing metrics consistent with those reported in previously established spectrophotometric methods.
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Celecoxib , Análise de Componente Principal , Espectrofotometria , Tramadol , Celecoxib/análise , Celecoxib/química , Tramadol/análise , Espectrofotometria/métodos , Calibragem , Reprodutibilidade dos Testes , Formas de Dosagem , Analgésicos Opioides/análiseRESUMO
Hypertension and hyperlipidemia are two common conditions that require effective management to reduce the risk of cardiovascular diseases. Among the medications commonly used for the treatment of these conditions, valsartan and pitavastatin have shown significant efficacy in lowering blood pressure and cholesterol levels, respectively. In this study, synchronous spectrofluorimetry coupled to chemometric analysis tools, specifically concentration residual augmented classical least squares (CRACLS) and spectral residual augmented classical least squares (SRACLS), was employed for the determination of valsartan and pitavastatin simultaneously. The developed models exhibited excellent predictive performance with relative root mean square error of prediction (RRMSEP) of 2.253 and 2.1381 for valsartan and pitavastatin, respectively. Hence, these models were successfully applied to the analysis of synthetic samples and commercial formulations as well as plasma samples with high accuracy and precision. Besides, the greenness and blueness profiles of the determined samples were also evaluated to assess their environmental impact and analytical practicability. The results demonstrated excellent greenness and blueness scores with AGREE score of 0.7 and BAGI score of 75 posing the proposed method as reliable and sensitive approach for the determination of valsartan and pitavastatin with potential applications in pharmaceutical quality control, bioanalytical studies, and therapeutic drug monitoring.
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Quinolinas , Espectrometria de Fluorescência , Valsartana , Quinolinas/química , Quinolinas/sangue , Valsartana/química , Valsartana/sangue , Análise dos Mínimos QuadradosRESUMO
The widespread dissemination of bacterial resistance has led to great attention being paid to finding substitutes for traditionally used antibiotics. Plants are rich in various phytochemicals that could be used as antibacterial therapies. Here, we elucidate the phytochemical profile of Euphorbia canariensis ethanol extract (EMEE) and then elucidate the antibacterial potential of ECEE against Pseudomonas aeruginosa clinical isolates. ECEE showed minimum inhibitory concentrations ranging from 128 to 512 µg/mL. The impact of ECEE on the biofilm-forming ability of the tested isolates was elucidated using crystal violet assay and qRT-PCR to study its effect on the gene expression level. ECEE exhibited antibiofilm potential, which resulted in a downregulation of the expression of the biofilm genes (algD, pelF, and pslD) in 39.13% of the tested isolates. The antibacterial potential of ECEE was studied in vivo using a lung infection model in mice. A remarkable improvement was observed in the ECEE-treated group, as revealed by the histological and immunohistochemical studies. Also, ELISA showed a noticeable decrease in the oxidative stress markers (nitric oxide and malondialdehyde). The gene expression of the proinflammatory marker (interleukin-6) was downregulated, while the anti-inflammatory biomarker was upregulated (interleukin-10). Thus, clinical trials should be performed soon to explore the potential antibacterial activity of ECEE, which could help in our battle against resistant pathogenic bacteria.
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Antibacterianos , Euphorbia , Extratos Vegetais , Pseudomonas aeruginosa , Infecções Respiratórias , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Euphorbia/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Animais , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Carga Bacteriana/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacosRESUMO
This research investigates the effects of the immunotherapeutic agent nivolumab on the metabolism of lung cancer cells (NCI-H1975) using GC-MS metabolomic profiling. Multivariate analysis such as unsupervised PCA and supervised OPLS-DA along with univariate analysis and pathway analysis were employed to explore the metabolomic data and identify altered metabolic pathways induced by nivolumab treatment. The study revealed distinct metabolic alterations in cancer cells, linked to proliferative and survival advantages, such as enhanced glycolysis, increased glutaminolysis, and modified amino acid metabolism. Key findings indicate elevated levels of glycolysis-related metabolites (glycine, alanine, pyruvate, and lactate) and TCA cycle intermediates (succinate, fumarate, malate) in cancer cells, with a significant decrease following nivolumab treatment. Additionally, lower levels of aspartic acid and citrate in cancer cells imply altered nucleotide synthesis and fatty acid production essential for tumor growth. Treatment with nivolumab also reduced oleic acid levels, indicative of its effect on disrupted lipid metabolism. Our research shows nivolumab's potential to modify metabolic pathways involved in lung cancer progression, suggesting its dual role in cancer therapy: as an immune response modulator and a metabolic pathway disruptor.
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Carcinoma Pulmonar de Células não Pequenas , Cromatografia Gasosa-Espectrometria de Massas , Neoplasias Pulmonares , Redes e Vias Metabólicas , Metabolômica , Nivolumabe , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nivolumabe/uso terapêutico , Nivolumabe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Metabolômica/métodos , Linhagem Celular Tumoral , Análise Multivariada , Redes e Vias Metabólicas/efeitos dos fármacos , Metaboloma/efeitos dos fármacosRESUMO
Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson's disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE's toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.
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Simeprevir and daclatasvir represent a cornerstone in the management of Hepatitis C Virus infection, a global health concern that affects millions of people worldwide. In this study, we propose a synergistic approach combining synchronous spectrofluorimetry and chemometric modeling i.e. Partial Least Squares (PLS-1) for the analysis of simeprevir and daclatasvir in different matrices. Moreover, the study employs firefly algorithms to further optimize the chemometric models via selecting the most informative features thus improving the accuracy and robustness of the calibration models. The firefly algorithm was able to reduce the number of selected wavelengths to 47-44% for simeprevir and daclatasvir, respectively offering a fast and sensitive technique for the determination of simeprevir and daclatasvir. Validation results underscore the models' effectiveness, as evidenced by recovery rates close to 100% with relative root mean square error of prediction (RRMSEP) of 2.253 and 2.1381 for simeprevir and daclatasvir, respectively. Moreover, the proposed models have been applied to determine the pharmacokinetics of simeprevir and daclatasvir, providing valuable insights into their distribution and elimination patterns. Overall, the study demonstrates the effectiveness of synchronous spectrofluorimetry coupled with multivariate calibration optimized by firefly algorithms in accurately determining and quantifying simeprevir and daclatasvir in HCV antiviral treatment, offering potential applications in pharmaceutical formulation analysis and pharmacokinetic studies for these drugs.
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Carbamatos , Imidazóis , Pirrolidinas , Simeprevir , Espectrometria de Fluorescência , Valina , Valina/análogos & derivados , Imidazóis/farmacocinética , Imidazóis/química , Valina/farmacocinética , Simeprevir/farmacocinética , Simeprevir/análise , Pirrolidinas/química , Carbamatos/farmacocinética , Análise dos Mínimos Quadrados , Espectrometria de Fluorescência/métodos , Algoritmos , Antivirais/farmacocinética , Reprodutibilidade dos TestesRESUMO
Hypertension and hyperlipidemia frequently coexist and are correlated with elevated cardiovascular adverse outcomes. Fixed dose combination tablets containing antihypertensive and antihyperlipidemic drugs have the potential to improve patient compliance. Telmisartan and rosuvastatin fixed dose combination tablet has been recently formulated. This study provided the first fluorescence spectroscopic method for simultaneously quantifying telmisartan and rosuvastatin in tablet dosage form and plasma. The native fluorescence spectra of telmisartan and rosuvastatin completely overlapped, making direct measurement unachievable. However, through the implementation of synchronous fluorescence measurements of telmisartan and rosuvastatin at a Δλ = 60, distinct narrow bands were observed at 358 nm and 375 nm, respectively. Regrettably, the challenge of overlapping remained unresolved. Nevertheless, by converting these synchronous spectra into first-order spectra, the problem of overlapping was completely resolved. This conversion also allowed for the selective quantification of telmisartan and rosuvastatin at 374 nm and 358 nm, respectively. The validity of this method was confirmed in accordance with ICH guidelines, yielding satisfactory results in terms of the validation characteristics. The method demonstrated linear relationships between the response and the studied drugs concentrations in working range of 50-1000 ng/mL for telmisartan and 100-2000 ng/mL for rosuvastatin. The described methodology was applied for the pharmacokinetic study of telmisartan and rosuvastatin in rat plasma after a single oral dose of 4 mg/kg telmisartan and 50 mg/kg rosuvastatin. Pharmacokinetic analyses revealed a moderate drug-drug interaction between the two drugs, which was not considered to be clinically significant. Moreover, the described method was assessed in terms of sensitivity and environmental sustainability against three previously documented methods. The comparison effectively underscores the supremacy of the proposed technique over the documented techniques.
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Anti-Hipertensivos , Humanos , Animais , Ratos , Rosuvastatina Cálcica , Telmisartan/efeitos adversos , Fluorescência , Comprimidos , Espectrometria de FluorescênciaRESUMO
This study assessed the ability of formulated curcumin-loaded chitosan nanoparticles (CU-CS-NPs) to reduce the kidney damage resulting from fenpropathrin (FPN) in rats compared to curcumin (CU) in rats. Sixty male Sprague Dawley rats were separated into six groups and orally administered 1 mL/kg b.wt corn oil, 50 mg CU/kg b.wt, 50 mg CU-CS-NPs /kg b.wt., 15 mg FPN /kg b.wt, CU+ FPN or CU-CS-NPs + FPN for 60 days. Then, serum renal damage products were assessed. Total antioxidant capacity, reactive oxygen species, interleukin 1ß (IL-1ß), malondialdehyde, NF-κB P65, cleaved-Caspase-1, and Caspase-8 were estimated in kidney homogenates. The cleaved Caspase-3 and TNF-α immunoexpression and pyroptosis-related genes were determined in renal tissues. The results showed that CU-CS-NPS significantly repressed the FPN-induced increment in kidney damage products (urea, uric acid, and creatinine). Moreover, the FPN-associated hypo-proteinemia, renal oxidative stress and apoptotic reactions, and impaired renal histology were considerably repaired by CU and CU-CS-NPs. Additionally, compared to FPN-exposed rats, CU, and CU-CS-NPs-treated rats had considerably lower immunoexpression of cleaved Caspase-3 and TNF-α in renal tissue. The pyroptosis-related genes NLRP3, GSDMD, IL-18, Caspase-3, Caspase-1, IL-1ß, Caspase-8, TNF-α, and NF-κB dramatically upregulated by FPN exposure in the renal tissues. Yet, in CU and CU-CS-NPs-treated rats, the gene above expression deviations were corrected. Notably, CU-CS-NPs were superior to CU in preventing oxidative damage and inflammation and regulating pyroptosis in the renal tissues of the FPN-exposed group. The results of the present study conclusively showed the superior favorable effect of CU-CS-NPs in counteracting renal impairment linked to environmental pollutants.
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Quitosana , Curcumina , Piretrinas , Piroptose , Animais , Masculino , Ratos , Caspase 1 , Caspase 3 , Caspase 8 , Curcumina/farmacologia , Rim , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piretrinas/toxicidade , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfaRESUMO
Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.
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Curcumina , Piretrinas , Humanos , Ratos , Animais , Curcumina/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estresse Oxidativo , Piretrinas/toxicidade , Apoptose , Corantes , PulmãoRESUMO
The present work is aimed to assess the protective influence of zinc oxide resveratrol nanoparticles against oxidative stress-associated testicular dysfunction. The number of 50 male albino rats were randomly separated into five groups (n = 10): Group I, control: rats gavage distilled water orally; Group II, Levofloxacin: rats that administered Levofloxacin (LFX) softened in distilled water at a dosage of 40 mg/kg-1 BW orally every other day; Group III, Zn-RSV: rats administered with Zn-RSV (zinc oxide resveratrol in distilled water at a dose 20 mg/kg-1 BW orally every other day; Group IV, (LFX + Zn-RSV): rats that were administered with Levofloxacin along with Zn-RSV nPs; Group V, Levofloxacin + Zn: rats were administered with Levofloxacin and Zno at a dose of 20 mg/kg-1 BW orally every other day as mentioned before. This study lasted for 2 months. Sera were collected to assess luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone values. Testicular tissues were utilized to evaluate levels of superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA), and catalase (CAT). Semen samples were utilized to measure their quality (motility, concentration, and vitality). Histopathological and immune histochemical techniques investigated the morphological changes in the testis. Rats treated with Levofloxacin showed significantly lower levels of serum LH, testosterone, FSH, testicular enzymatic NO, catalase, SOD, BAX, and BCL-2 immune reactivity and sperm quality but significantly greater testicular malondialdehyde and caspase-3 immuno-reactivity Compared to both control and zinc oxide resveratrol treatment. Zinc oxide resveratrol nanoparticles ameliorated the harmful side effects of Levofloxacin. Improvements were more pronounced in the co-treatment (LFX + Zn-RSV) Zinc oxide resveratrol group than in the co-treatment (LFX + Zno) Zinc oxide group. Zinc oxide resveratrol nanoparticles could be a possible solution for levofloxacin oxidative stress-induced fertility problems.
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Nanopartículas , Doenças Testiculares , Óxido de Zinco , Humanos , Ratos , Masculino , Animais , Resveratrol/farmacologia , Resveratrol/metabolismo , Óxido de Zinco/farmacologia , Catalase/metabolismo , Levofloxacino/farmacologia , Ratos Wistar , Sêmen , Testículo/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Testosterona , Hormônio Foliculoestimulante , Hormônio Luteinizante , Superóxido Dismutase/metabolismo , Malondialdeído/metabolismo , Água/metabolismoRESUMO
BACKGROUND: Diabetes mellitus is a complex metabolic disorder with systemic implications, necessitating the search for reliable biomarkers and therapeutic strategies. This study investigates the metabolomics profile alterations in diabetic rats, with a focus on the therapeutic effects of Dapagliflozin, a drug known to inhibit renal glucose reabsorption, using Gas Chromatography-Mass Spectrometry analysis. METHODS: A GC-MS based metabolomics approach combined with multivariate and univariate statistical analyses was utilized to study serum samples from a diabetic model of Wistar rats, treated with dapagliflozin. Metabolomics pathways analysis was also performed to identify the altered metabolic pathways associated with the disease and the intervention. RESULTS: Dapagliflozin treatment in diabetic rats resulted in normalized levels of metabolites associated with insulin resistance, notably branched-chain and aromatic amino acids. Improvements in glycine metabolism were observed, suggesting a modulatory role of the drug. Additionally, reduced palmitic acid levels indicated an alleviation of lipotoxic effects. The metabolic changes indicate a restorative effect of dapagliflozin on diabetes-induced metabolic perturbations. CONCLUSIONS: The comprehensive metabolomics analysis demonstrated the potential of GC-MS in revealing significant metabolic pathway alterations due to dapagliflozin treatment in diabetic model rats. The therapy induced normalization of key metabolic disturbances, providing insights that could advance personalized diabetes mellitus management and therapeutic monitoring, highlighting the utility of metabolomics in understanding drug mechanisms and effects.
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Compostos Benzidrílicos , Diabetes Mellitus Experimental , Glucosídeos , Ratos , Animais , Cromatografia Gasosa-Espectrometria de Massas/métodos , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos Wistar , Metabolômica/métodos , Análise MultivariadaRESUMO
This study presents the development of an eco-friendly and highly selective mitrogen-doped carbon quantum dot based sensor (N-CQDs) for the detection of gabapentin - a commonly misused drug. A detailed characterization of N-CQDs spectral features and their interaction with gabapentin is provided. The optimal conditions for sensing, including pH value, buffer volume, N-CQDs concentration, and incubation time, were established. The results showed excellent fluorescence quenching at 475 nm (λex = 380 nm) due to the dynamic quenching mechanism, and the sensor demonstrated excellent linearity in the 0.5-8.0 µg mL-1 concentration range with correlation coefficients of more than 0.999, a limit of detection (LOD) of 0.160 and limit of quantification (LOQ) of 0.480 µg mL-1. The accuracy of the proposed sensor was acceptable with a mean accuracy of 99.91 for gabapentin detection. In addition, precision values were within the acceptable range, with RSD% below 2% indicating good repeatability and reproducibility of the sensor. Selectivity was validated using common excipients and pooled plasma samples. The proposed sensor accurately estimated gabapentin concentration in commercial pharmaceutical formulations and spiked plasma samples, exhibiting excellent comparability with previously published methods. The 'greenness' of the sensing system was evaluated using the Analytical GREEnness calculator, revealing low environmental impact and strong alignment with green chemistry principles with a greenness score of 0.76. Thus, the developed N-CQDs-based sensor offers a promising, eco-friendly, and effective tool for gabapentin detection in various situations, ranging from clinical therapeutics to forensic science.
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The coronavirus disease 2019 (COVID-19) was first found in Wuhan, China, in December 2019. Because the virus spreads quickly, it quickly became a global worry. Coronaviridae is the family that contains both SARS-CoV-2 and the viruses that came before (i.e., MERS-CoV and SARS-CoV). Recent sources portray that the COVID-19 virus has affected 344,710,576 people worldwide and killed about 5,598,511 people in the last 2 years. The B.1.1.529 strain, later called "Omicron," was named a Variant of Concern on November 24, 2021. The SARS-CoV-2 virus has gone through a never-ending chain of changes that have never happened before. As a result, it has many different traits. Most of these changes have occurred in the spike protein, where antibodies bind. Because of these changes, the Omicron type is very contagious and easy to pass on. There have been a lot of studies done to try to figure out this new challenge in the COVID-19 strains race, but there is still a lot that needs to be explained. This study focuses on virtual screening, docking, and molecular dynamic analysis; we aimed to identify therapeutic candidates for the SARS-CoV-2 variant Omicron based on their ability to inhibit non-structural proteins. We investigate the prediction of the properties of a substantial database of drug molecules obtained from the OliveNet™ database. Compounds that did not exhibit adequate gastrointestinal absorption and failed the Lipinski test are not considered for further research. The filtered compounds were coupled with our primary target, SARS-CoV-2 Omicron spike protein. We focused on SARS-CoV-2 Omicron spike protein and filtering potent olive compounds. Pinoresinol, the most likely candidate, is bound best (- 8.5 kcal/mol). Pinoresinol's strong interaction with the active site made the complex's dynamic structure more resilient. MD simulations explain the protein-ligand complex's stability and function. Pinoresinol may be a promising SARS-CoV-2 Omicron spike protein receptor lead drug, and additional research may assist the scientific community.
Assuntos
COVID-19 , Furanos , Lignanas , Olea , SARS-CoV-2 , Humanos , Simulação de Dinâmica Molecular , Glicoproteína da Espícula de CoronavírusRESUMO
Wound healing is a significant healthcare problem that decreases the patient's quality of life. Hence, several agents and approaches have been widely used to help accelerate wound healing. The challenge is to search for a topical delivery system that could supply long-acting effects, accurate doses, and rapid healing activity. Topical forms of simvastatin (SMV) are beneficial in wound care. This study aimed to develop a novel topical chitosan-based platform of SMV with folic acid (FA) for wound healing. Moreover, the synergistic effect of combinations was determined in an excisional wound model in rats. The prepared SMV-FA-loaded films (SMV-FAPFs) were examined for their physicochemical characterizations and morphology. Box-Behnken Design and response surface methodology were used to evaluate the tensile strength and release characteristics of the prepared SMV-FAPFs. Additionally, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction pattern (XRD), and animal studies were also investigated. The developed SMV-FAPFs showed a contraction of up to 80% decrease in the wound size after ten days. The results of the quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant upregulation of dermal collagen type I (CoTI) expression and downregulation of the inflammatory JAK3 expression in wounds treated with SMV-FAPFs when compared to control samples and individual drug treatments. In summary, it can be concluded that the utilization of SMV-FAPFs holds great potential for facilitating efficient and expeditious wound healing, hence presenting a feasible substitute for conventional topical administration methods.
RESUMO
Treating wound infections is a challenging concern in various clinical settings in Egypt, especially in the increasing global problem of resistance to antimicrobials. Here, we aimed to fabricate CuO NPs via green synthesis using aqueous Yucca gigantea extract. Then, the effect of green synthesized CuO NPs on Staphylococcus aureus clinical isolates has been studied in vivo and in vitro. The aqueous extract of Yucca gigantea has been employed in our study as a scale-up approach to safely, affordably, sustainably, and practically fabricate copper oxide nanoparticles (CuO NPs). Fourier transforms infrared (FT-IR), X-ray Diffraction (XRD), and UV-vis spectroscopy were utilized in vitro to describe the bonding features of CuO NPs.Scanning Electron microscopy (SEM), Transmission electron microscopy (TEM), Energy dispersive X-ray (EDX), and dynamic light scattering (DLS) were used to detect the morphological and elemental composition of the resulting CuO NPs. The fabrication of CuO NPs was confirmed by the IR spectral band at 515 cm-1, ensuring the metal-oxygen bondCu-O with two strong bands at 229 and 305 nm. SEM and TEM show CuO NPs with a size range from 30 to 50 nm. Cu and O comprised most of the particles produced through green synthesis, with weight percentages of 57.82 and 42.18 %, respectively. CuO NPs were observed to have a Zeta-potential value of -15.7 mV, demonstrating their great stability. CuO NPs revealed antibacterial potential toward the tested isolates with minimum inhibitory concentration values of 128 to 512 µg/mL. CuO NPs had antibiofilm potential by crystal violet assay, downregulating the expression of icaA and icaD genes in 23.07 % and 19.32 of the S. aureus isolates. The wound-healing potential of CuO NPs was investigated in vivo. It significantly decreased the bacterial burden and increased wound healing percentage compared to the positive control group. Moreover, CuO NPs caused an upregulation of the genes encoding platelet-derived growth factor (PDGF) and fibronectin in tissue repair. Thus, we can use CuO NPs as a future source for wound healing materials, especially in infected wounds.