RESUMEN
Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.
Asunto(s)
Lipopolisacáridos , Trastornos de la Memoria , Enfermedades Neuroinflamatorias , Condicionamiento Físico Animal , Ratas Wistar , Animales , Masculino , Lipopolisacáridos/toxicidad , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Ratas , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/inducido químicamente , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Entrenamiento de Fuerza/métodos , Corteza Cerebral/metabolismo , Corteza Cerebral/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Receptor Muscarínico M1/metabolismoRESUMEN
Curcumin is an active polyphenol substance found in the highest concentrations in the roots of Curcuma longa. Its health benefits have led to recent increases in the consumption of curcumin. It has anti-inflammatory and antioxidant activities and is a potent neuroprotective against diseases of the brain. Nevertheless, its low bioavailability and its relative difficulty crossing the blood-brain barrier limit curcumin's use for these purposes. Curcumin-loaded nanoparticles may be an effective treatment for several diseases although there is a paucity of studies reporting its safety in the central nervous system (CNS). Therefore, this study aimed to identify non-neurotoxic concentrations of free curcumin and two nanoformulations of curcumin. Cell lines BV-2 and SH-SY5Y, both originating from the CNS, were evaluated after 24, 48, and 72 h of treatment with free curcumin and nanocapsules We measured viability, proliferation, and dsDNA levels. We measured levels of reactive oxygen species and nitric oxide as proxies for oxidative stress in culture supernatants. We found that free curcumin was toxic at 10 and 20 µM, principally at 72 h. Nanoformulations were more neurotoxic than the free form. Safe concentrations of free curcumin are between 1-5 µM, and these concentrations were lower for nanoformulations. We determined the ideal concentrations of free curcumin and nanocapsules serving as a basis for studies of injuries that affect the CNS.
Asunto(s)
Curcumina , Nanocápsulas , Neuroblastoma , Humanos , Curcumina/farmacología , Nanocápsulas/toxicidad , Línea Celular , Estrés OxidativoRESUMEN
Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, and its congenital transmission is of paramount concern. During embryonic development, infection with the parasite causes irreversible damage to the still-forming fetus's central nervous system (CNS). In the pathogenesis of neurotoxoplasmosis, purinergic receptors prejudice neuroprotection, neuroinflammation, and activation of microbicide mechanisms against the parasitic vacuole. This study used curcumin as a treatment for neural precursor cells (NPCs) infected with T. gondii. The congenital toxoplasmosis induction consisted of maternal infection with the VEG strain, and NPCs were obtained from the telencephalon of mouse embryos. Curcumin at increasing concentrations was administered in vitro to analyze NPC metabolic activity, cell number, and size, as well as neurogliogenesis, proving to be effective in recovering the size of infected NPCs. Curcumin partially re-established impaired neurogenesis. Purinergic A1, A2A, and P2X7 receptors may be related to neuroprotection, neuroinflammatory control, and activation of mechanisms for inducing the parasite's death. ERK 1/2 was highly expressed in infected cells, while its expression rates decreased after the addition of the treatment, highlighting the possible anti-inflammatory action of curcumin. These findings suggest that curcumin treats neurological perturbations induced by toxoplasmosis.
Asunto(s)
Curcumina , Células-Madre Neurales , Toxoplasma , Toxoplasmosis Cerebral , Toxoplasmosis Congénita , Femenino , Embarazo , Animales , Ratones , Toxoplasma/fisiología , Curcumina/farmacología , Toxoplasmosis Congénita/parasitologíaRESUMEN
The objective of this work was to produce and characterise nanoemulsions containing tucumã extract and to evaluate the performance of the nanostructure and the free compound regarding antitumor activity, cytotoxicity, and oxidative metabolism in NB4/APL cells. The nanoemulsions showed adequate physicochemical characteristics (average size approx. 200 nm, polydispersity index less than 0.3, negative zeta potential and acid pH) maintained stable up to 90 days of storage in refrigeration condition. The nanoformulations did not present protein corona formation. Blank nanoemulsion treatments showed moderate toxicity. Furthermore, the nanoemulsion loaded with extract showed better antileukemic results than the free extract. However, nanoemulsions can be promising carriers of natural compounds, emphasising their biological properties and constituting alternatives in treating diseases.
Asunto(s)
Arecaceae , Nanoestructuras , Antioxidantes/química , Emulsiones/química , Nanoestructuras/químicaRESUMEN
In this work was to develop an inedited nanocapsule with tucumã oil (Astrocaryum vulgare). The oil presents of phytosterols (squalene and ß-sitosterol), all-trans-beta-carotene, acids oleic and palmitic. Antioxidant activity showed a good performance in DPPH and ABTS assays. The nanocapsules were prepared and demonstrated in their characterization particle size (206 ± 0.69 nm). The cytogenotoxicity evaluation was performed using the MTT, dichlorofluorescein, nitric oxide and dsDNA PicoGreen® assays. Antitumor efficacy assays in MCF-7 cells demonstrated that free oil and tucumã nanocapsules had IC50 of 130 and 50 µg/mL, respectively. Thus, previous studies of toxicity are relevant, as they generate future subsidies, aiming at the potential application of nanostructures and in addition, the promising effect of NCs of tucumã oil on the antiproliferative effect in breast adenocarcinoma cells was evidenced.
Asunto(s)
Antioxidantes/farmacología , Arecaceae/química , Nanocápsulas/química , Fitoquímicos/farmacología , Aceites de Plantas/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/análisis , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Células MCF-7 , Tamaño de la Partícula , Fitoquímicos/análisis , Fitosteroles/análisis , Aceites de Plantas/químicaRESUMEN
Mancozeb is a fungicide widely used in agriculture, mostly against the pathogen Glomerella cingulata responsible for the rot of ripe grape, but presents high toxicity. Strategies are sought to reduce the toxicity of this fungicide and alternative treatments are welcome. An alternative could be the use of clove oil, which has Eugenol as its major compound, and has antifungal potential against G. cingulata, however, Eugenol is susceptible to degradation processes which may compromise its efficacy. The nanoencapsulation of Mancozeb and Eugenol is a possible strategy to overcome the limitations of toxicity, solubility and instability of these compounds. Therefore, the objective of this study is to develop nanoemulsions containing Mancozeb (0.1â¯mg/mL) and Eugenol (33â¯mg/mL), isolated or associated, and evaluate the safety of these formulations through cytotoxicity, genotoxicity and ecotoxicity tests. Nanoemulsions were developed by the spontaneous emulsification method, cytotoxicity and genotoxicity were evaluated in healthy human cells through MTT, Dichlorofluorescein diacetate and Picogreen tests, and ecotoxicity assessment was carried out using the chronic toxicity test in springtails. After preparation, the physicochemical characterization of the nanoemulsions were performed which presented mean particle size between 200 and 300â¯nm, polydispersity index less than 0.3, negative zeta potential and acid pH. The nanoencapsulation was able to avoid the reduction of the cell viability caused by Mancozeb, while Eugenol was shown to be safe for cell use in both free and nanostructured forms, however the association of the two active compounds showed toxicity in the higher doses of Mancozeb. In the ecotoxicity tests, both free Mancozeb and Eugenol forms presented high toxic potential for soil, whereas the nanoencapsulation of these compounds did not cause a reduction in number of springtails. Therefore, from the tests performed, it was possible to observe that nanoencapsulation of Mancozeb and Eugenol is a safe alternative for the application of these compounds mainly in agriculture.
Asunto(s)
Artrópodos/efectos de los fármacos , Daño del ADN , Eugenol/toxicidad , Fungicidas Industriales/toxicidad , Maneb/toxicidad , Nanocápsulas/toxicidad , Zineb/toxicidad , Animales , Artrópodos/crecimiento & desarrollo , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Emulsiones , Eugenol/química , Fungicidas Industriales/química , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Maneb/química , Nanocápsulas/química , Tamaño de la Partícula , Phyllachorales/efectos de los fármacos , Suelo/química , Pruebas de Toxicidad , Zineb/químicaRESUMEN
Tetra-platinated(II) porphyrin hexafluorophosphate compound (4-PtTPyPor) was synthetized and along 5,10,15,20-tetrakis(4-pyridyl)porphyrin (4-TPyPor), evaluated about the antimicrobial activity and safety. The effect was evaluated with and without light exposition. The antimicrobial activity was analyzed by microdilution and growth curve method. The assays showed an increase of antimicrobial potential caused by porphyrins with light exposition comparing the treatment without light irradiation. The biocompatibility was tested by MTT, ROS production, dsDNA on culture medium and hemolysis. All platinum porphyrin concentrations showed hemolytic activity under light exposition. The ROS measurement doesn't showed statistic difference between treatments and control. The picogreen assay demonstrates a reduction of dsDNA on culture medium with cells treated with porphyrins under light irradiation. The study demonstrated that the platinated porphyrins might be promising microbial photodynamic inactivation with potential applications in wastewater treatment, biofilm control and bioremediation.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Platino (Metal)/farmacología , Porfirinas/farmacología , Antibacterianos/química , Bacterias/crecimiento & desarrollo , Bacterias/efectos de la radiación , Medios de Cultivo , ADN Bacteriano/análisis , Hemólisis , Luz , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Platino (Metal)/química , Porfirinas/química , Especies Reactivas de Oxígeno/metabolismo , Factores de Tiempo , Aguas Residuales , Purificación del Agua/métodosRESUMEN
Biofilms are considered important sources of infections on biomedical surfaces, and most infections involving biofilm formation are associated with medical device implants. Therefore, there is an urgent need for new antimicrobial compounds that can combat microbial resistance associated with biofilm formation. In this context, this work aimed to evaluate the antibiofilm action of sulfamethoxazole complexed with Au, Cd, Cu, Ni and Hg on rapidly growing mycobacteria (RGM), as well as to evaluate their safety through cytotoxic assays. The results demonstrate potentiation of the novel compounds in antibiofilm activity, mainly in the complex with Au, which was able to completely inhibit biofilm formation and had the capacity to destroy the biofilm at all the concentrations tested. All cytotoxic data suggest that the majority of sulfamethoxazole metallic derivatives are antimicrobial alternatives, as well as safe molecules, which could be used as potential therapeutic agents for bacterial and biofilm elimination.