RESUMO
Melanoma has gained considerable attention due to its high mortality and morbidity rate worldwide. The currently available treatment options are associated with several limitations such as nonspecificity, drug resistance, easy clearance, low efficacy, toxicity-related issues, etc. To this end, nanotechnology has garnered significant attention for the treatment of melanoma. In the present manuscript, we have demonstrated the in vitro and in vivo anticancer activity of silver nitroprusside nanoparticles (abbreviated as AgNNPs) against melanoma. The AgNNPs exhibit cytotoxicity against B16F10 cells, which has been investigated by several in vitro experiments including [methyl 3H]-thymidine incorporation assay, cell cycle and apoptosis analysis by flow cytometry, and ROS generation through DCFDA, DHE, and DAF2A reagents. Further, the internalization of nanoparticles was determined by ICPOES analysis, while their colocalization was analyzed by confocal microscopy. Additionally, JC-1 staining is performed to examine mitochondrial membrane potential (MMP). Cytoskeleton integrity was observed by phalloidin staining. Expression of different markers (Ki-67, cytochrome c, and E-cadherin) was checked using an immunofluorescence assay. The in vivo therapeutic efficacy of AgNNPs has been validated in the melanoma model established by inoculating B16F10 cells into the dorsal right abdomen of C57BL/6J mice. The intraperitoneal administration of AgNNPs reduced melanoma growth and increased the survivability of tumor-bearing mice. The in vivo immunofluorescence studies (Ki-67, CD31, and E-cadherin) and TUNEL assay support the inhibitory and apoptotic nature of AgNNPs toward melanoma, respectively. Furthermore, the various signaling pathways and molecular mechanisms involved in anticancer activity are evaluated by Western blot analysis. These findings altogether demonstrate the promising anticancer potential of AgNNPs toward melanoma.
Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos Endogâmicos C57BL , Nitroprussiato , Prata , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Nitroprussiato/farmacologia , Nitroprussiato/química , Apoptose/efeitos dos fármacos , Prata/química , Prata/farmacologia , Proliferação de Células/efeitos dos fármacos , Tamanho da Partícula , Teste de Materiais , Melanoma/tratamento farmacológico , Melanoma/patologia , Nanopartículas Metálicas/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nanopartículas/química , Sobrevivência Celular/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Melanoma Experimental/metabolismoRESUMO
Cut flowers deteriorate rapidly after harvest, lasting mere days. To extend their vase life, various postharvest techniques are employed. Due to limited knowledge about the postharvest physiology of Alstroemeria cut flowers and the specific role of secondary compounds and antioxidant systems in their protection, this study investigated the optimal dosage of sodium nitroprusside (SNP) as a nitric oxide (NO) donor to enhance quality and antioxidant defenses. Preharvest foliar application of SNP at 0, 50, 100, and 200 µM followed by short-term pulsing treatments upon harvest at the same concentrations were applied in a factorial design. Results revealed that a preharvest 100 µM SNP treatment combined with a 50 µM postharvest pulse significantly increased the total amount of phenols (over 20%), antioxidant capacity (more than doubled), and the activity of two antioxidant enzymes (ascorbate peroxidase by over 35% and guaiacol peroxidase by about 20%). Notably, this combination also diminished ion leakage (by about 20%), ultimately extending the vase life by more than 40% compared to untreated plants. Therefore, SNP application at these specific dosages proves effective in bolstering Alstroemeria cut flower quality and vase life through enhanced total phenols and a strengthened antioxidant system.
Assuntos
Antioxidantes , Flores , Nitroprussiato , Nitroprussiato/farmacologia , Flores/efeitos dos fármacos , Flores/fisiologia , Antioxidantes/metabolismo , Fenóis/metabolismo , Doadores de Óxido Nítrico/farmacologia , Peroxidase/metabolismo , Ascorbato Peroxidases/metabolismoRESUMO
Melanoma is the most invasive and lethal form of skin cancer that arises from the malignant transformation of specialized pigment-producing cell melanocytes. Nanomedicine represents an important prospect to mitigate the difficulties and provide significant benefits to cure melanoma. In the present study, we investigated in vitro and in vivo therapeutic efficacies of copper nitroprusside analogue nanoparticles (abbreviated as CuNPANP) towards melanoma. Initially, in vitro anti-cancer activities of CuNPANP towards melanoma cells (B16F10) were evaluated by several experiments such as [methyl-3H]-thymidine incorporation assay, cell cycle and apoptosis assays using FACS analysis, ROS generation using DCFDA, DHE and DAF2A reagents, internalization of nanoparticles through ICP-OES analysis, co-localization of the nanoparticles using confocal microscopy, JC-1 staining to investigate the mitochondrial membrane potential (MMP) and immunofluorescence studies to analyze the expressions of cytochrome-c, Ki-67, E-cadherin as well as phalloidin staining to analyze the cytoskeletal integrity. Further, the in vivo therapeutic effectiveness of the nanoparticles was established towards malignant melanoma by inoculating B16F10 cells in the dorsal right abdomen of C57BL/6J mice. The intraperitoneal administration of CuNPANP inhibited tumor growth and increased the survivability of melanoma mice. The in vivo immunofluorescence studies (Ki-67, CD-31, and E-cadherin) and TUNEL assay further support the anti-cancer and apoptosis-inducing potential of CuNPANP, respectively. Finally, various signaling pathways and molecular mechanisms involved in anti-cancer activities were further evaluated by Western blot analysis. The results altogether indicated the potential use of copper-based nanomedicines for the treatment of malignant melanoma.
Assuntos
Apoptose , Cobre , Melanoma Experimental , Camundongos Endogâmicos C57BL , Nitroprussiato , Animais , Camundongos , Linhagem Celular Tumoral , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Melanoma Experimental/metabolismo , Apoptose/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Nitroprussiato/farmacologia , Nitroprussiato/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Nanopartículas/química , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Proliferação de Células/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêuticoRESUMO
Skin wound infection has become a notable medical threat. Herein, the polysaccharide-based injectable hydrogels with multifunctionality were developed by a simple and fast gelation process not only to inactivate bacteria but also to accelerate bacteria-infected wound healing. Sodium nitroprusside (SNP) loaded PCN-224 nanoparticles were introduced into the polymer matrix formed by the dynamic and reversible coordinate bonds between Ag+ with carboxyl and amino or hydroxyl groups on carboxymethyl chitosan (CMCS), hydrogen bonds and electrostatic interactions in the polymer to fabricate SNP@PCN@Gel hydrogels. SNP@PCN@Gel displayed interconnected porous structure, excellent self-healing capacity, low cytotoxicity, good blood compatibility, and robust antibacterial activity. SNP@PCN@Gel could produce reactive oxygen species (ROS) and NO along with Fe2+, and showed long-term sustained release of Ag+, thereby effectively killing bacteria by synergistic photothermal (hyperthermia), photodynamic (ROS), chemodynamic (Fenton reaction), gas (NO) and ion (Ag+ and -NH3+ in CMCS) therapy. Remarkably, the hydrogels significantly promoted granulation tissue formation, reepithelization, collagen deposition and angiogenesis as well as wound contraction in bacteria-infected wound healing. Taken together, the strategy represented a general method to engineer the unprecedented photoactivatable "all-in-one" hydrogels with enhanced antibacterial activity and paved a new way for development of antibiotic alternatives and wound dressing.
Assuntos
Antibacterianos , Quitosana , Hidrogéis , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Animais , Nitroprussiato/farmacologia , Nitroprussiato/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Prata/química , Prata/farmacologia , Nanopartículas/química , Infecção dos Ferimentos/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
Despite the considerable efforts reported so far to enhance seed priming, novel ideas are still needed to be suggested to this sustainable sector of agri-seed industry. This could be the first study addressing the effect of nitric oxide (NO) under open field conditions. The impacts of seed redox-priming using sodium nitroprusside (SNP) and osmo-priming with calcium chloride (CaCl2), both applied individually or successively, were investigated under salinity stress conditions on wheat plants (Triticum aestivum L.). Various parameters, including water relations, growth, yield, photosynthetic pigments, and antioxidant activities (enzymatic and non-enzymatic), were recorded to assess the outcomes of these priming agents on mitigating the negative impacts of salinity stress on wheat plants. Water consumptive use (ETa) and irrigation water applied (IWA) decreased with seeds priming. Successive priming with SNP + CaCl2 induced the greatest values of crop water productivity (CWP), irrigation water productivity (IWP), seed index, grain yield and grain nitrogen content.Under salinity stress, the dry weight of plants was decreased. However, hydro-priming and successive chemical priming agents using combinations of calcium chloride and sodium nitroprusside (CaCl2 + SNP & SNP + CaCl2) preserved growth under salinity stress.Individual priming with sodium nitroprusside (SNP) and calcium chloride (CaCl2) resulted in the lowest recorded content of sodium in the shoot, with a value of 2 ppm. On the other hand, successive priming using CaCl2 + SNP or SNP + CaCl2 induced the contents of potassium in the shoot, with values of 40 ppm and 39 ppm, respectively. Malondialdehyde decreased in shoot significantly withapplicationof priming agents. Successive priming with CaCl2 + SNP induced the highest proline contents in shoot (6 µg/ g FW). The highest value of phenolics and total antioxidants contents in shoot were recorded under successive priming using CaCl2 + SNP and SNP + CaCl2.Priming agents improved the activities of ascorbate peroxidase and catalase enzymes. The successive priming improved water relations (ETa, IWA, CWP and IWP) and wheat growth and productivity under salinity stress more than individual priming treatments.
Assuntos
Antioxidantes , Cloreto de Cálcio , Óxido Nítrico , Nitroprussiato , Espécies Reativas de Oxigênio , Tolerância ao Sal , Triticum , Triticum/metabolismo , Triticum/efeitos dos fármacos , Triticum/fisiologia , Triticum/crescimento & desenvolvimento , Antioxidantes/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Cloreto de Cálcio/farmacologia , Nitroprussiato/farmacologia , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Sementes/fisiologia , Sementes/metabolismo , Cálcio/metabolismoRESUMO
Sodium nitroprusside (SNP) is a potent nitric oxide (NO) donor that enhances plant tolerance to various abiotic stresses. This research aims to assess the effect of SNP application on rice seedlings subjected to individual and combined exposure to two abiotic stresses viz., low-temperature (LT) and chromium (Cr). Exposure to LT, Cr, and LT+Cr caused severe oxidative damage by stimulating greater production and accumulation of reactive oxygen species (ROS) leading to lipid peroxidation and cell membrane instability. The combined LT+CR stress more intensly increased the cellular oxidative stress and excessive Cr uptake that in turn deteriorated the chlorophyll pigments and photosynthesis, as well as effected the level of tetrapyrrole biosynthesis in rice plants. The reduction in rice seedling growth was more obvious under LT+Cr treatment than their individual effects. The exogenous application of SNP diminished the toxic impact of LT and Cr stress. This was attributed to the positive role of SNP in regulating the endogenous NO levels, free amino acids (FAAs) contents, tetrapyrrole biosynthesis and antioxidants. Consequently, SNP-induced NO decreased photorespiration, ROS generation, lipid peroxidation, and electrolyte leakage. Moreover, exogenous SNP diminished the Cr uptake and accumulation by modulating the ionic homeostasis and strengthening the heavy metals detoxification mechanism, thus improving plant height, biomass and photosynthetic indexes. Essentially, SNP boosts plant tolerance to LT and Cr stress by regulating antioxidants, detoxification mechanism, and the plant's physio-biochemical. Hence, applying SNP is an effective method for boosting rice plant resilience and productivity in the face of escalating environmental stresses and pollutants.
Assuntos
Antioxidantes , Cromo , Temperatura Baixa , Homeostase , Óxido Nítrico , Oryza , Oxirredução , Fotossíntese , Oryza/metabolismo , Oryza/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fotossíntese/efeitos dos fármacos , Antioxidantes/metabolismo , Homeostase/efeitos dos fármacos , Cromo/farmacologia , Oxirredução/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Nitroprussiato/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
Experimental glomerulonephritis results in hypertension that is sensitive to salt. Nevertheless, salt retention alone cannot explain the increase in blood pressure. Angiotensin antagonistic therapy reduces hypertension caused by puromycin amino nucleosides (PAN). We investigated the hypothesis that PAN modifies renal vascular reactivity through processes dependent on angiotensin. Long-Evans rats were given an intraperitoneal injection of either puromycin (150 mg/kg) or saline (controls). Group 1 was fed a normal sodium diet (NSD, n = 9). Group 2 was given 30 mg/L of quinapril (Q) in addition to NSD (NSD + Q; n = 6). Group 3 received a high sodium diet (HSD, n = 7), and Group 4 received HSD + Q (n = 7). Systolic blood pressure (SBP), plasma creatinine, proteinuria, and sodium balance were monitored for 12 days. On day 15, renal vascular reactivity was assessed by administering increasing doses of angiotensin II, acetylcholine (ACh), and sodium nitroprusside (SNP) directly into the renal artery. SBP progressively increased in all PAN groups. This increase in SBP was greater in the HSD groups and was not significantly altered by Q treatment. SBP increased by 22 ± 4% (NSD), 51 ± 5% (NSD + Q), 81 ± 10% (HSD), and 65 ± 8% (HSD + Q). The renal blood flow of PAN rats did not return to baseline despite their normal renal vasoconstrictor responses to angiotensin II. Additionally, they showed reduced renal vasodilator responses to SNP and Ach. The vasodilator responses to both vasodilators were surprisingly unaffected by the inhibition of the angiotensin-converting enzyme (ACE). Renal vasodilator responses to both endothelium-dependent and independent variables were reduced in early PAN-induced hypertension. We found that the angiotensin-mediated mechanism is not responsible for this altered renal vasoreactivity.
Assuntos
Angiotensina II , Rim , Animais , Angiotensina II/farmacologia , Ratos , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Masculino , Ratos Long-Evans , Pressão Sanguínea/efeitos dos fármacos , Puromicina/farmacologia , Nitroprussiato/farmacologia , Puromicina Aminonucleosídeo , Acetilcolina/farmacologia , Nefropatias/induzido quimicamenteAssuntos
Nicardipino , Nitroprussiato , Humanos , Nicardipino/uso terapêutico , Nicardipino/economia , Nitroprussiato/economia , Nitroprussiato/uso terapêutico , Recém-Nascido , Pressão Sanguínea/efeitos dos fármacos , Anti-Hipertensivos/economia , Anti-Hipertensivos/uso terapêutico , Lactente , Vasodilatadores/economia , Vasodilatadores/uso terapêuticoRESUMO
The clinical application of doxorubicin (DOX) is mainly restricted by its serious side effects, poor drug delivery efficiency, and limited immunogenic death (ICD) effect. To improve DOX-based chemotherapy and ameliorate its adverse effects, we utilized 3LL cell-derived extracellular vesicles to encapsulate DOX and sodium nitroprusside (SNP) to obtain DOX/SNP@CM, which could effectively target the tumor site by harnessing the inherent homologous targeting property of tumor cell membranes. DOX performed its role on chemotherapy, and SNP successfully respond to the intracellular GSH to continuously generate nitric oxide (NO). The in situ-produced NO upregulated the Fas expression on the tumor cell surface, thereby sensitizing the Fas/FasL pathway-mediated tumor cell apoptosis of DOX. Furthermore, NO also boosted the intratumoral infiltration of cytotoxic T cells by promoted ICD effect towards tumor cells. Importantly, the anti-tumor immunity tightly cooperated with Fas/FasL mediated tumor cell apoptosis by NO-mediated manipulation on Fas/FasL interaction, collectively making DOX/SNP@CM exert significant tumor growth inhibition with low-dose DOX. Remarkably, DOX and SNP both are widely used clinical medicines, ensuring DOX/SNP@CM a potential opportunity for future practical applications.
Assuntos
Antibióticos Antineoplásicos , Apoptose , Doxorrubicina , Vesículas Extracelulares , Proteína Ligante Fas , Nitroprussiato , Receptor fas , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Proteína Ligante Fas/metabolismo , Receptor fas/metabolismo , Animais , Nitroprussiato/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Óxido Nítrico/metabolismo , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/imunologia , Humanos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Sistemas de Liberação de Medicamentos/métodosRESUMO
In various neurodegenerative conditions, inflammation plays a significant role in disrupting the blood-brain barrier (BBB), contributing to disease progression. Nitric oxide (NO) emerges as a central regulator of vascular function, with a dual role in inflammation, acting as both a pro- and anti-inflammatory molecule. This study investigates the effects of the NO donor sodium nitroprusside (SNP) in protecting the BBB from lipopolysaccharide (LPS)-induced inflammation, using bEnd.3 endothelial cells as a model system. Additionally, Raw 264.7 macrophages were employed to assess the effects of LPS and SNP on their adhesion to a bEnd.3 cell monolayer. Our results show that LPS treatment induces oxidative stress, activates the JAK2/STAT3 pathway, and increases pro-inflammatory markers. SNP administration effectively mitigates ROS production and IL-6 expression, suggesting a potential anti-inflammatory role. However, SNP did not significantly alter the adhesion of Raw 264.7 cells to bEnd.3 cells induced by LPS, probably because it did not have any effect on ICAM-1 expression, although it reduced VCAM expression. Moreover, SNP did not prevent BBB disruption. This research provides new insights into the role of NO in BBB disruption induced by inflammation.
Assuntos
Barreira Hematoencefálica , Inflamação , Lipopolissacarídeos , Nitroprussiato , Lipopolissacarídeos/farmacologia , Nitroprussiato/farmacologia , Animais , Camundongos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Células RAW 264.7 , Inflamação/patologia , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Estresse Oxidativo/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Adesão Celular/efeitos dos fármacos , Interleucina-6/metabolismo , Transdução de Sinais/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Inflammation and oxidative stress upset memory. We explored influence of sodium nitroprusside (SNP) on memory deficits resulted from lipopolysaccharide (LPS).Groups include control, LPS, LPS + SNP 1 mg/kg, LPS + SNP 2 mg/kg, and LPS + SNP 3 mg/kg. Morris water maze and passive avoidance tests and biochemical measurements were carried out.In Morris water maze, LPS prolonged time and distance for finding the platform. In probe trial, it diminished time spent and traveled distance in the target zone. Injection of 2 and 3 mg/kg of SNP overturned the effect of LPS. In passive avoidance task, LPS postponed entrance into darkroom and reduced time spent in light room and incremented time spent in darkroom in 3, 24, and 72 h after electrical shock. All three doses of SNP restored the effects of LPS. Biochemical experiments confirmed that LPS elevated interleukin-6 and malondialdehyde concentration and declined total thiol content and superoxide dismutase and catalase activity in the hippocampus and cortex tissues. SNP particularly at a 3 mg/kg dose ameliorated LPS effects on these parameters.SNP attenuated memory disabilities resulting from LPS through modifying inflammation and boosting antioxidant defense.
Assuntos
Lipopolissacarídeos , Transtornos da Memória , Nitroprussiato , Estresse Oxidativo , Ratos Wistar , Animais , Lipopolissacarídeos/toxicidade , Nitroprussiato/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Transtornos da Memória/metabolismo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacosRESUMO
Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.
Assuntos
Células Fotorreceptoras Retinianas Cones , Degeneração Retiniana , Sciuridae , Tomografia de Coerência Óptica , Animais , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologia , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Modelos Animais de Doenças , Injeções Intravítreas , Oftalmoscopia , Nitroprussiato/farmacologia , Feminino , MasculinoAssuntos
Nitroprussiato , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/tratamento farmacológico , Feminino , Masculino , Nitroprussiato/administração & dosagem , Nitroprussiato/uso terapêutico , Nitroprussiato/farmacologia , Adulto , Adulto Jovem , Resultado do Tratamento , Adolescente , Escalas de Graduação PsiquiátricaRESUMO
KEY MESSAGE: Sodium nitroprusside mediates drought stress responses in tomatoes by modulating nitrosative and oxidative pathways, highlighting the interplay between nitric oxide, hydrogen sulfide, and antioxidant systems for enhanced drought tolerance. While nitric oxide (NO), a signalling molecule, enhances plant tolerance to abiotic stresses, its precise contribution to improving tomato tolerance to drought stress (DS) through modulating oxide-nitrosative processes is not yet fully understood. We aimed to examine the interaction of NO and nitrosative signaling, revealing how sodium nitroprusside (SNP) could mitigate the effects of DS on tomatoes. DS-seedlings endured 12% polyethylene glycol (PEG) in a 10% nutrient solution (NS) for 2 days, then transitioned to half-strength NS for 10 days alongside control plants. DS reduced total plant dry weight, chlorophyll a and b, Fv/Fm, leaf water potential (ΨI), and relative water content, but improved hydrogen peroxide (H2O2), proline, and NO content. The SNP reduced the DS-induced H2O2 generation by reducing thiol (-SH) and the carbonyl (-CO) groups. SNP increased not only NO but also the activity of L-cysteine desulfhydrase (L-DES), leading to the generation of H2S. Decreases in S-nitrosoglutathione reductase (GSNOR) and NADPH oxidase (NOX) suggest a potential regulatory mechanism in which S-nitrosylation [formation of S-nitrosothiol (SNO)] may influence protein function and signaling pathways during DS. Moreover, SNP improved ascorbate (AsA) and glutathione (GSH) and reduced oxidized glutathione (GSSG) levels in tomato plants under drought. Furthermore, the interaction of NO and H2S, mediated by L-DES activity, may serve as a vital cross-talk mechanism impacting plant responses to DS. Understanding these signaling interactions is crucial for developing innovative drought-tolerance strategies in crops.
Assuntos
Secas , Peróxido de Hidrogênio , Óxido Nítrico , Nitroprussiato , Solanum lycopersicum , Nitroprussiato/farmacologia , Solanum lycopersicum/fisiologia , Solanum lycopersicum/metabolismo , Solanum lycopersicum/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Glutationa/metabolismo , Antioxidantes/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/fisiologia , Plântula/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/fisiologia , Nitrosação/efeitos dos fármacos , Clorofila/metabolismoRESUMO
Considering the high recrudescence and the long-lasting unhealed large-sized wound that affect the aesthetics and cause dysfunction after resection of maxillofacial malignant skin tumors, a groundbreaking strategy is urgently needed. Photothermal therapy (PTT), which has become a complementary treatment of tumors, however, is powerless in tissue defect regeneration. Therefore, a novel multifunctional sodium nitroprusside and Fe2+ ions loaded microneedles (SNP-Fe@MNs) platform was fabricated by accomplishing desirable NIR-responsive photothermal effect while burst releasing nitric oxide (NO) after the ultraviolet radiation for the ablation of melanoma. Moreover, the steady releasing of NO in the long term by the platform can exert its angiogenic effects via upregulating multiple related pathways to promote tissue regeneration. Thus, the therapeutic dilemma caused by postoperative maxillofacial skin malignancies could be conquered through promoting tumor cell apoptosis via synergistic PTT-gas therapy and subsequent regeneration process in one step. The bio-application of SNP-Fe@MNs could be further popularized based on its ideal bioactivity and appealing features as a strategy for synergistic therapy of other tumors occurred in skin.
Assuntos
Melanoma , Óxido Nítrico , Terapia Fototérmica , Neoplasias Cutâneas , Animais , Terapia Fototérmica/métodos , Camundongos , Neoplasias Cutâneas/terapia , Melanoma/terapia , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Linhagem Celular Tumoral , Agulhas , Humanos , Nitroprussiato/farmacologia , Apoptose/efeitos dos fármacos , Pele , Ferro/química , Raios UltravioletaRESUMO
Burns are a significant public health issue worldwide, resulting in prolonged hospitalization, disfigurement, disability and, in severe cases, death. Among them, deep second-degree burns are often accompanied by bacterial infections, insufficient blood flow, excessive skin fibroblasts proliferation and collagen deposition, all of which contribute to poor wound healing and scarring following recovery. In this study, SNP/MCNs-SKN-chitosan-ß-glycerophosphate hydrogel (MSSH), a hydrogel composed of a temperature-sensitive chitosan-ß-glycerophosphate hydrogel matrix (CGH), mesoporous carbon nanospheres (MCNs), nitric oxide (NO) donor sodium nitroprusside (SNP) and anti-scarring substance shikonin (SKN), is intended for use as a biomedical material. In vitro tests have revealed that MSSH has broad-spectrum antibacterial abilities and releases NO in response to near-infrared (NIR) laser to promote angiogenesis. Notably, MSSH can inhibit excessive proliferation of fibroblasts and effectively reduce scarring caused by deep second-degree burns, as demonstrated by in vitro and in vivo tests.
Assuntos
Queimaduras , Cicatriz , Hidrogéis , Naftoquinonas , Cicatrização , Queimaduras/tratamento farmacológico , Queimaduras/patologia , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Cicatriz/prevenção & controle , Cicatriz/patologia , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Naftoquinonas/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Fibroblastos/efeitos dos fármacos , Quitosana/farmacologia , Quitosana/química , Temperatura , Camundongos , Humanos , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Proliferação de Células/efeitos dos fármacosAssuntos
Insuficiência Cardíaca , Nitroprussiato , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/induzido quimicamente , Nitroprussiato/efeitos adversos , Nitroprussiato/administração & dosagem , Doença Aguda , Vasodilatadores/efeitos adversos , Vasodilatadores/administração & dosagem , AnimaisRESUMO
The present study examined the regulatory mechanism of hydrogen sulfide (H2S) and nitric oxide (NO) in nickel (Ni) stressed cyanobacteria viz., Nostoc muscorum and Anabaena sp. by analyzing growth, photosynthetic pigments, biochemical components (protein and carbohydrate), exopolysaccharides (EPS), inorganic nitrogen content, and activity of enzymes comprised in nitrogen metabolism and Ni accumulation. The 1 µM Ni substantially diminished growth by 18% and 22% in N. muscorum and Anabaena sp. respectively, along with declining the pigment contents (Chl a/Car ratio and phycobiliproteins), and biochemical components. It also exerted negative impacts on inorganic uptake of nitrate and nitrite contents; nitrate reductase and nitrite reductase; and ammonium assimilating enzymes (glutamine synthetase, glutamate synthase, and glutamate dehydrogenase exhibited a reverse trend) activities. Nonetheless, the adverse impact of Ni can be mitigated through the exogenous supplementation of NaHS [sodium hydrosulfide (8 µM); H2S donor] and SNP [sodium nitroprusside (10 µM); NO donor] which showed substantial improvement on growth, pigments, nitrogen metabolism, and EPS layer and noticeably occurred as a consequence of a substantial reduction in Ni accumulation content which minimized the toxicity effects. The accumulation of Ni on both the cyanobacterial cell surface (EPS layer) are confirmed by the SEM-EDX analysis. Further, the addition of NO scavenger (PTIO; 20 µM) and inhibitor of NO (L-NAME; 100 µM); and H2S scavenger (HT; 20 µM) and H2S inhibitor (PAG; 50 µM) reversed the positive responses of H2S and NO and damages were more prominent under Ni stress thereby, suggesting the downstream signaling of H2S on NO-mediated alleviation. Thus, this study concludes the crosstalk mechanism of H2S and NO in the mitigation of Ni-induced toxicity in rice field cyanobacteria.
Assuntos
Sulfeto de Hidrogênio , Níquel , Óxido Nítrico , Nitrogênio , Oryza , Óxido Nítrico/metabolismo , Níquel/metabolismo , Sulfeto de Hidrogênio/metabolismo , Nitrogênio/metabolismo , Oryza/metabolismo , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Nostoc muscorum/metabolismo , Polissacarídeos Bacterianos/metabolismo , Anabaena/metabolismo , Anabaena/efeitos dos fármacos , Anabaena/crescimento & desenvolvimento , Estresse Fisiológico , Nitroprussiato/farmacologiaRESUMO
Endothelial dysfunction develops with age and may precede cardiovascular disease. Animal data suggest that T-type calcium channels play an important role in endothelial function, but data from humans are lacking. This study included 15 healthy, sedentary, elderly males for a double blinded, randomized controlled trial. For 8 weeks, they were given 40 mg/day of either efonidipine (L- and T-type calcium channel blocker (CCB)) or nifedipine (L-type CCB). Vascular function was evaluated by graded femoral arterial infusions of acetylcholine (ACh; endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator) both with and without co-infusion of N-acetylcysteine (NAC; antioxidant). We measured leg blood flow and mean arterial pressure and calculated leg vascular conductance to evaluate the leg vascular responses. Despite no significant change in blood pressure in either group, we observed higher leg blood flow responses (Δ 0.43 ± 0.45 l/min, P = 0.006) and leg vascular conductance (Δ 5.38 ± 5.67 ml/min/mmHg, P = 0.005) to intra-arterial ACh after efonidipine, whereas there was no change in the nifedipine group, and no differences between groups. We found no upregulation of endothelial nitric oxide synthase in vastus lateralis muscle biopsies within or between groups. Smooth muscle cell responsiveness was unaltered by efonidipine or nifedipine. Intravenous co-infusion of NAC did not affect endothelium-dependent vasodilatation in either of the CCB groups. These results suggest that 8 weeks' inhibition of T- and L-type calcium channels augments endothelium-dependent vasodilatory function in healthy elderly males. Further studies are required to elucidate if T-type calcium channel inhibition can counteract endothelial dysfunction.
Assuntos
Bloqueadores dos Canais de Cálcio , Canais de Cálcio Tipo T , Endotélio Vascular , Nifedipino , Nitrofenóis , Humanos , Masculino , Canais de Cálcio Tipo T/metabolismo , Canais de Cálcio Tipo T/efeitos dos fármacos , Idoso , Bloqueadores dos Canais de Cálcio/farmacologia , Nifedipino/farmacologia , Projetos Piloto , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Di-Hidropiridinas/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Compostos Organofosforados/farmacologia , Acetilcolina/farmacologia , Perna (Membro)/irrigação sanguínea , Nitroprussiato/farmacologia , Pessoa de Meia-IdadeRESUMO
We sought to investigate possible impaired hyperaemia during dynamic handgrip exercise (HGE) in young healthy individuals who had recovered from COVID-19. We tested the vascular function in individuals recovered from COVID-19 using a nitric oxide donor (i.e., sodium nitroprusside; SNP), which could revert a possible impaired endothelial function during HGE. Further, we tested whether individuals who recovered from COVID-19 would present exaggerated brachial vascular resistance under an adrenergic agonist (i.e., phenylephrine; PHE) stimuli during HGE. Participants were distributed into two groups: healthy controls (Control; men: n = 6, 30 ± 3 years, 26 ± 1 kg/m2; and women: n = 5, 25 ± 1 years, 25 ± 1 kg/m2) and subjects recovered from COVID-19 (post-COVID; men: n = 6, 29 ± 3 years, 25 ± 1 kg/m2; and women: n = 10, 32 ± 4 years, 22 ± 1 kg/m2). Participants in the post-COVID group tested positive (RT-PCR) 12-14 weeks before the protocol. Heart rate (HR), brachial blood pressure (BP), brachial blood flow (BBF) and vascular conductance (BVC) at rest were not different between groups. The HGE increased HR (Control: Δ9 ± 0.4 bpm; and post-COVID: Δ11 ± 0.4 bpm) and BP (Control: Δ6 ± 1 mmHg; and post-COVID: Δ12 ± 0.6 mmHg) in both groups. Likewise, BBF (Control: Δ632 ± 38 ml/min; and post-COVID: Δ620 ± 27 ml/min) and BVC (Control: Δ6.6 ± 0.4 ml/min/mmHg; and post-COVID: Δ6.1 ± 0.3 ml/min/mmHg) increased during HGE. SNP did not change HGE-induced hyperaemia but did decrease BP, which induced a reflex-related increase in HR. PHE infusion also did not change the HGE-induced hyperaemia but raised BP and reduced HR. In conclusion, exercise-induced hyperaemia is preserved in healthy young subjects 12-14 weeks after recovery from COVID-19 infection.