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1.
Molecules ; 26(4)2021 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-33672652

RESUMEN

Herein, we report the neuroprotective and antioxidant activity of 1,1'-biphenyl nitrones (BPNs) 1-5 as α-phenyl-N-tert-butylnitrone analogues prepared from commercially available [1,1'-biphenyl]-4-carbaldehyde and [1,1'-biphenyl]-4,4'-dicarbaldehyde. The neuroprotection of BPNs1-5 has been measured against oligomycin A/rotenone and in an oxygen-glucose deprivation in vitro ischemia model in human neuroblastoma SH-SY5Y cells. Our results indicate that BPNs 1-5 have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN), and they are quite similar to N-acetyl-L-cysteine (NAC), which is a well-known antioxidant agent. Among the nitrones studied, homo-bis-nitrone BPHBN5, bearing two N-tert-Bu radicals at the nitrone motif, has the best neuroprotective capacity (EC50 = 13.16 ± 1.65 and 25.5 ± 3.93 µM, against the reduction in metabolic activity induced by respiratory chain blockers and oxygen-glucose deprivation in an in vitro ischemia model, respectively) as well as anti-necrotic, anti-apoptotic, and antioxidant activities (EC50 = 11.2 ± 3.94 µM), which were measured by its capacity to reduce superoxide production in human neuroblastoma SH-SY5Y cell cultures, followed by mononitrone BPMN3, with one N-Bn radical, and BPMN2, with only one N-tert-Bu substituent. The antioxidant activity of BPNs1-5 has also been analyzed for their capacity to scavenge hydroxyl free radicals (82% at 100 µM), lipoxygenase inhibition, and the inhibition of lipid peroxidation (68% at 100 µM). Results showed that although the number of nitrone groups improves the neuroprotection profile of these BPNs, the final effect is also dependent on the substitutent that is being incorporated. Thus, BPNs bearing N-tert-Bu and N-Bn groups show better neuroprotective and antioxidant properties than those substituted with Me. All these results led us to propose homo-bis-nitrone BPHBN5 as the most balanced and interesting nitrone based on its neuroprotective capacity in different neuronal models of oxidative stress and in vitro ischemia as well as its antioxidant activity.


Asunto(s)
Antioxidantes/farmacología , Óxidos N-Cíclicos/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Lipooxigenasa/metabolismo , Fármacos Neuroprotectores/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Óxidos N-Cíclicos/síntesis química , Óxidos N-Cíclicos/química , Humanos , Radical Hidroxilo/antagonistas & inhibidores , Peroxidación de Lípido/efectos de los fármacos , Inhibidores de la Lipooxigenasa/síntesis química , Inhibidores de la Lipooxigenasa/química , Estructura Molecular , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Células Tumorales Cultivadas
2.
Food Chem ; 352: 129458, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-33714166

RESUMEN

We investigated the effect of exogenous glutathione (GSH) on chilling injury (CI) in postharvest bell pepper fruits stored at low temperature and explored the mechanism of this treatment from the perspective of the ascorbate-glutathione (AsA-GSH) cycle. Compared with the control, fruits treated with exogenous GSH before refrigeration displayed only slight CI symptoms and mitigated CI-induced cell damage after 10 d. Moreover, the treated peppers had lower lipid peroxidation product, H2O2, and O2- content than those did the control. Glutathione treatment enhanced the ascorbate-glutathione cycle by upregulating CaAPX1, CaGR2, CaMDHAR1, and CaDHAR1 and the antioxidant enzymes APX, GR, and MDHAR associated with the ascorbate-glutathione cycle. Glutathione treatment also increased ascorbate and glutathione concentrations. Taken together, our results showed that exogenous GSH treatment could alleviate CI in pepper fruits during cold storage by triggering the AsA-GSH cycle and improving antioxidant capacity.


Asunto(s)
Ácido Ascórbico/metabolismo , Capsicum/efectos de los fármacos , Capsicum/metabolismo , Frío , Glutatión/farmacología , Frutas/efectos de los fármacos , Frutas/metabolismo , Glutatión/metabolismo , Peróxido de Hidrógeno/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/metabolismo
3.
Medicine (Baltimore) ; 100(8): e24811, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663100

RESUMEN

BACKGROUND: We performed a randomized clinical trial protocol to assess the effectiveness of edaravone for acute stroke. We hypothesized that edaravone is beneficial in improving neurological impairment resulting from acute stroke. METHOD: The protocol was reviewed and approved by the Research Ethics Board of Affiliated Hospital of Chengde Medical University (0092-2394), each participant signed a written consent before participating, and SPIRIT guidelines were followed throughout. The inclusion criteria for patients were as follows: diagnosed as acute stroke (ischemic stroke or intracerebral hemorrhage) by head CT or MRI within 72 hours; age greater than 18; motor function disorder; Glasgow Coma Scale greater than 12. Patients with the following symptoms were excluded: concurrent serious complications, such as coma, drug allergy, mental disorder, and other severe organic lesions in the brain. Sixty patients were finally included in the study. The control group accepted conventional treatment, while the treatment group received edaravone treatment on top of the conventional treatment of the control group. After treatment, the differences in functional movement, living ability score, neurological score, treatment effect, and adverse reaction of these 2 groups were tested and compared. DISCUSSION: As aging worsens, the incidence of acute stroke continues to increase. Brain damage will induce the production of oxygen radicals, which can damage the cytomembrane of brain cells and finally damage the nervous system and cause cerebral injury as well as the cerebral edema. Edaravone is an antioxidant and oxygen radical scavenger that can inhibit lipid peroxidation during the scavenging of oxygen free radicals. Besides, it can also elicit anti-inflammatory protective effects for nerve cells, increase cerebral blood flow volume, prevent the aggravation of cerebral hypoperfusion toward necrosis, reduce nerve damage, and improve neurological functions and prognosis. This is the first randomized controlled trial to assess the efficacy of edaravone for treating acute stroke. High quality, large sample size, multicenter randomized trials are still required. TRIAL REGISTRATION: researchregistry6492.


Asunto(s)
Edaravona/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Actividades Cotidianas , Circulación Cerebrovascular/efectos de los fármacos , Edaravona/farmacología , Femenino , Depuradores de Radicales Libres/farmacología , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Fármacos Neuroprotectores/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
Int J Nanomedicine ; 16: 1757-1773, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33688190

RESUMEN

Background: NiO nanoparticles have attracted much attention due to their unique properties. They have been synthesized using chemical and physical techniques that often need toxic chemicals. These toxic chemicals cannot easily be removed from the nanoparticle's surface, make them less biocompatible, and limit their biological applications. Instead, plants based green synthesis of nanoparticles uses phytomolecules as reducing and capping agents. These phytomolecules are biologically active with no or less toxic effects. Materials and Methods: Phytomolecules-coated NiO nanoparticles were synthesized employing a green route using Abutilon indicum leaf extract. For comparative study, we also have synthesized NiO nanoparticles using the co-precipitation method. Synthesized nanoparticles were successfully characterized using different spectroscopic techniques. The synthesized nanoparticles were evaluated for antibacterial activity with agar well diffusion assay against different bacteria compared to standard drug and plant extract. They are also examined for anticancer potential using MTT assay against HeLa cancer cells, and further, their antioxidant potential was determined using DPPH assay. Biocompatibility of the synthesized nanoparticles was assessed against fibroblast cells. Results: Phytomolecules-coated NiO nanoparticles were demonstrated superior antibacterial and anticancer performance against bacteria (E. coli, B. bronchiseptica, B. subtilis, and S. aureus) by presenting highest zone of inhibitions (18 ± 0.58 mm, 21 ± 0.45 mm, 22 ± 0.32 mm, and 23 ± 0.77 mm) and HeLa cancer cells by exhibiting the least cell viability percentage (51.74 ± 0.35%) compared to plant extract and chemically synthesized NiO nanoparticles but were comparable to standard antibiotic and anticancer drugs, respectively. Phytomolecules-coated NiO nanoparticles were also demonstrated excellent antioxidant activity (79.87 ± 0.43% DPPH inhibition) and biocompatibility (> 90% cell viability) with fibroblast cells. Conclusion: Nanoparticle synthesis using the Abutilon indicum leaf extract is an efficient and economical method, produces biocompatible and more biologically active nanoparticles, which can be an excellent candidate for therapeutic applications.


Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Malvaceae/química , Nanopartículas del Metal/química , Fitoquímicos/química , Extractos Vegetales/química , Hojas de la Planta/química , Bacterias/efectos de los fármacos , Compuestos de Bifenilo/química , Fibroblastos/efectos de los fármacos , Tecnología Química Verde , Células HeLa , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana , Picratos/química , Espectrometría por Rayos X , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Difracción de Rayos X
5.
Molecules ; 26(4)2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33672029

RESUMEN

Exposure to reactive oxygen species can easily result in serious diseases, such as hyperproliferative skin disorders or skin cancer. Herbal extracts are widely used as antioxidant sources in different compositions. The importance of antioxidant therapy in inflammatory conditions has increased. Innovative formulations can be used to improve the effects of these phytopharmacons. The bioactive compounds of Plantago lanceolata (PL) possess different effects, such as anti-inflammatory, antioxidant, and bactericidal pharmacological effects. The objective of this study was to formulate novel liquid crystal (LC) compositions to protect Plantago lanceolata extract from hydrolysis and to improve its effect. Since safety is an important aspect of pharmaceutical formulations, the biological properties of applied excipients and blends were evaluated using assorted in vitro methods on HaCaT cells. According to the antecedent toxicity screening evaluation, three surfactants were selected (Gelucire 44/14, Labrasol, and Lauroglycol 90) for the formulation. The dissolution rate of PL from the PL-LC systems was evaluated using a Franz diffusion chamber apparatus. The antioxidant properties of the PL-LC systems were evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and malondialdehyde (MDA) assessments. Our results suggest that these compositions use a nontraditional, rapid-permeation pathway for the delivery of drugs, as the applied penetration enhancers reversibly alter the barrier properties of the outer stratum corneum. These excipients can be safe and highly tolerable thus, they could improve the patient's experience and promote adherence.


Asunto(s)
Composición de Medicamentos , Cristales Líquidos/química , Extractos Vegetales/farmacología , Plantago/química , Piel/efectos de los fármacos , Compuestos de Bifenilo/química , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Impedancia Eléctrica , Depuradores de Radicales Libres/farmacología , Humanos , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/efectos de la radiación , Malondialdehído/metabolismo , Permeabilidad , Picratos/química , Piel/efectos de la radiación , Rayos Ultravioleta
6.
Food Funct ; 12(5): 2090-2101, 2021 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-33554990

RESUMEN

Plant-based polyphenols are increasingly being explored as functional ingredients in emulsified food systems. In this study, the effects of sesamol on the physical and chemical stability of flaxseed oil-in-water emulsions stabilized by either phospholipids (sunflower) or proteins (whey or pea) were investigated. In the absence of sesamol, the protein-based emulsions displayed better physical stability than the phospholipid-based ones, which was related to their smaller particle diameter and higher particle charge. For the phospholipid-based emulsions, sesamol addition did not improve their physical stability, but it did inhibit lipid oxidation. In particular, it decreased the formation of secondary oxidation products, with a 65% reduction in TBAR formation compared to the control after 8 days of storage. For the protein-based emulsions, sesamol addition reduced particle aggregation and inhibited lipid oxidation, reducing the secondary oxidation products by around 85% after 19 days of storage. The inhibitory efficiency of sesamol in the pea protein-based emulsions was comparable to that in the whey protein-based ones. The effects of sesamol on the physical and chemical stability of the emulsions were related to its partitioning between the oil, water, and interfacial layers. This study suggests that adding sesamol to plant-based emulsions may improve their physical and chemical stability, thereby extending their shelf life.


Asunto(s)
Benzodioxoles/farmacología , Emulsiones/química , Aceite de Linaza/química , Fenoles/farmacología , Fosfolípidos/química , Proteínas/química , Agua/química , Antioxidantes/farmacología , Fenómenos Químicos , Estabilidad de Medicamentos , Peroxidación de Lípido/efectos de los fármacos , Oxidación-Reducción , Proteínas de Guisantes/química , Proteína de Suero de Leche/química
7.
Aquat Toxicol ; 233: 105771, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33578303

RESUMEN

Present study aims to investigate interaction of molecular chaperons (heat shock protein 70, heat shock protein 90) with transcriptional factors (nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1) to evaluate their role during metal induced stress in fish hepatocytes. Adult Puntius ticto were exposed to lead nitrate at 0 mg/l (control), 1/50th (0.04 mg/l) and 1/20th (0.12 mg/l) of LC50 for 30 days and sacrificed to collect liver tissues. Activity of selected liver enzymes, antioxidants and metallothionein were analyzed. Levels of heat shock protein 70, heat shock protein 90, nuclear factor kappa B, nuclear factor E2-related factor 2 and Kelch-like ECH-associated protein 1 were also measured. Liver enzymes showed a significant increase (p < 0.05) in both Pb exposed groups indicating that the liver might be at risk of damage. Increased level of lipid peroxidation due to metal stress was marked by significant increase (p < 0.05) in malondialdehyde level in fish exposed to the higher Pb concentration compared to control (+ 13.7 %). Significant increase (p < 0.05) in gluthathione reductase (+ 35 %, + 39.2 %), glutathione s-transferase (+ 22.4 %, + 50.4 %) activities and decrease in reduced glutathione level (- 6.75 %, - 12.25 %) in fish exposed to both lower and higher Pb concentration compared to control also indicated metal induced oxidative damage in fish liver. Super oxide dismutase and catalase activities increased significantly (p < 0.05) during exposure to lower Pb concentration, while decreased significantly (p < 0.05) during exposure to higher Pb concentration compared to those in control. Significant (P < 0.05) increase (+ 52.63 %, + 89.47 %) in metallothionein in Pb exposed groups confirmed its role in detoxification process of the metal. Heat shock protein 70 and heat shock protein 90 expression levels increased significantly (p < 0.05) during metal exposure indicating their role as modulator of stress-induced antioxidant protein remodelling. A positive correlation between nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1 with gluthathione regulatory enzymes (gluthathione reductase and glutathione s-transferase) was noted. Current study effectively illuminates the critical role of different factors (heat shock proteins/nuclear factor kappa B/nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1) to influence the expression and synthesis of antioxidants and other functional enzymes in lead-exposed fish liver.


Asunto(s)
Antioxidantes/metabolismo , Cyprinidae/metabolismo , Proteínas de Choque Térmico/metabolismo , Plomo/toxicidad , Hígado/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Contaminantes Químicos del Agua/toxicidad , Animales , Peroxidación de Lípido/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Nitratos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal
8.
Life Sci ; 270: 119146, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33545199

RESUMEN

Deferasirox (DFX) was formulated into oil-in-water microemulsions in the presence of pluronicto improve its oral bioavailability. The size of the DFX-loadedmicroemulsions system measured by dynamic light scattering (DLS) was about 9 nm. The anti-proliferative and anti-lipid peroxidation effects of DFX and DFX-loaded microemulsions were assessed on Human umbilical vein endothelial (HUVEC) cells. Our in vitro results showed that HUVEC cells are more susceptible to free DFX as compared to DFX-loaded microemulsions. Although both free and encapsulated DFX attenuated FeCl3-induced lipid peroxidation, after 6 and 12 h treatment, DFX-loaded microemulsions did not appear a better ameliorator than DFX. To compare the in vivo efficacy of free DFX and DFX-loaded microemulsions in iron- intoxicated rats, the animals were orally administered with 25 mg/kg DFX, or 25 mg/kg DFX microemulsions, respectively. In vivo gavage handling of free DFX significantly increased serum biochemical parameters. There was also a significant increase in lipid peroxidation in rats who received free DFX compared to those in the control rats. Treatment with DFX-loaded microemulsions restored the elevated levels of serum AST, ALT, and creatinine levels and also reduced liver MDA content. Histopathological analysis of renal and hepatic tissues was in line with the biochemical results. In conclusion, DFX-loaded microemulsions induce less toxicity than free DFX and appear a more desirable and safer drug carrier in combating the iron-overload complications. Theoretical simulations are performed to get better insight regarding interactions between DFX and surfactant F127.


Asunto(s)
Deferasirox/farmacología , Sistemas de Liberación de Medicamentos/métodos , Sobrecarga de Hierro/tratamiento farmacológico , Animales , Deferasirox/metabolismo , Emulsiones/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hierro/análisis , Hierro/metabolismo , Hierro/toxicidad , Quelantes del Hierro/farmacología , Sobrecarga de Hierro/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Micelas , Ratas , Ratas Wistar
9.
Ecotoxicol Environ Saf ; 213: 112052, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33631635

RESUMEN

The hatchability, mortality rate, lipid peroxide levels, and swimming speed of Artemia salina have been compared based on short exposures of ZnCl2, CdCl2, and HgCl2 in artificial seawater. The hatching tests were carried out for 12, 24, 36, and 48 h at 28 °C. Mortality rate and lipid peroxide (LPO) levels were determined after 24 h of exposure at 28 °C, in the dark, and on living larvae using the FOX method. The swimming speed was determined after 24 h using a microcomputer coupled to a digital camera, with simultaneous treatment of the recorded images every 25 s, at 25 °C, under red-light irradiation. Results showed that Zn caused a gradual inhibition of the hatching for concentrations <900 µmol L-1; however, Cd and Hg displayed almost complete inhibition for concentrations ≤100 µmol L-1. Also, the heavy metals caused a dose-dependent increase of mortality (LD50) in the following order: Zn = 3290 µmol L-1 < Cd = 2206 µmol L-1 < Hg = 15.6 µmol L-1. Furthermore, significant LPO levels were found for Cd (1500-2000 µmol L-1, p < 0.001) and Hg (5-20 µmol L-1, p < 0.001). Finally, the swimming speed values increased significantly, for Zn ≈ 2.5 mm s-1 (1500 µmol L-1, p < 0.001), Cd ≈ 3.5 mm s-1 (2000 µmol L-1, p < 0.05), and Hg ≈ 4.0 mm s-1 (15 µmol L-1, p < 0.05), after 24 h exposure. There is a clear dose-dependent toxicity, indicating that Zn, Cd and Hg can induce significant changes in hatchability, mortality, and ethological and biochemical parameters.


Asunto(s)
Artemia/fisiología , Metales Pesados/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Cadmio , Larva , Peroxidación de Lípido/efectos de los fármacos , Mercurio , Agua de Mar , Natación
10.
Int J Nanomedicine ; 16: 1037-1050, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603367

RESUMEN

Purpose: Hepatocellular carcinoma (HCC) is one of the most common fatal cancers, with no curative therapy available. The concept of ferroptosis is attracting increasing attention in cancer research. Herein, we describe the use of a nanodevice as an effective strategy for inducing ferroptosis to manage HCC. Methods: To improve ferroptosis-induced treatment of HCC, we constructed sorafenib (sor)-loaded MIL-101(Fe) nanoparticles (NPs) [MIL-101(Fe)@sor] and evaluated the efficacy of ferroptosis-based HCC therapy after co-administration with the iRGD peptide both in vitro and in vivo. Results: The prepared MIL-101(Fe) NPs have several promising characteristics including drug-loading, controllable release, peroxidase activity, biocompatibility, and T2 magnetic resonance imaging ability. MIL-101(Fe)@sor NPs significantly induced ferroptosis in HepG2 cells, increased the levels of lipid peroxidation and malondialdehyde, and reduced those of glutathione and glutathione peroxidase 4 (GPX-4). The in vivo results showed that the MIL-101(Fe)@sor NPs significantly inhibited tumor progression and decreased GPX-4 expression levels, with negligible long-term toxicity. Meanwhile, co-administration of MIL-101(Fe)@sor NPs with iRGD significantly accelerated ferroptosis. Conclusion: Our findings suggest that MIL-101(Fe)@sor NPs co-administered with iRGD are a promising strategy for inducing HCC ferroptosis.


Asunto(s)
Ferroptosis , Hierro/química , Neoplasias Hepáticas/tratamiento farmacológico , Estructuras Metalorgánicas/química , Oligopéptidos/administración & dosificación , Oligopéptidos/uso terapéutico , Sorafenib/administración & dosificación , Sorafenib/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Endocitosis/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Células Hep G2 , Humanos , Peroxidación de Lípido/efectos de los fármacos , Neoplasias Hepáticas/patología , Estructuras Metalorgánicas/ultraestructura , Ratones , Nanopartículas/química , Nanopartículas/toxicidad , Nanopartículas/ultraestructura , Peroxidasa/metabolismo , Conejos , Sorafenib/farmacología , Pruebas de Toxicidad
11.
Molecules ; 26(1)2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33466302

RESUMEN

Marantodes pumilum (MP) is a great source of herbal medicine used traditionally by both men and women for various purposes. MP may have potential wound-healing effects due to its diverse biological properties. An extensive study was conducted in a normal male rat model for determining the effects of MP var. pumila (MPvp) and var. alata (MPva) on the wound healing process. Here, 126 male Sprague-Dawley rats were divided randomly into seven groups as follows: sham-operated (SH), vehicle dressing (VD), flavine dressing (FD), MPvp leaves (PL), MPvp roots (PR), MPva leaves (AL), and MPva roots (AR). The parameters studied were the percentage of wound contraction, histomorphology study by hematoxylin and eosin (H&E), Masson-Goldner trichrome (MGT), and immunohistochemistry (IHC) staining. In addition, the levels of enzymatic antioxidants and malondialdehyde were also measured in the wound tissue homogenates. Wounds treated with extracts (PL, PR, AL, and AR) showed significantly faster healing (p < 0.05) compared to untreated and control groups (SH, VD, and FD). Histological analysis among MP-treated groups revealed better re-epithelialization, higher collagen deposition, enhanced fibronectin content and fibroblast cells, and higher fiber transformation from collagen-III to collagen-I, accompanied with a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. MP has antioxidant effects that may enhance wound healing in the rat model.


Asunto(s)
Antioxidantes/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Hojas de la Planta/química , Primulaceae/química , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/análisis , Ratas , Ratas Sprague-Dawley , Piel/lesiones
12.
Aquat Toxicol ; 231: 105737, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33422861

RESUMEN

Increasing global research has identified microplastics (MPs) to be impacting marine organisms. The present work aimed at investigating the physiological and behavioral effects of thirty-six juvenile Sparus aurata exposed to control, virgin and weathered MPs enriched diets during a 21-day period under controlled conditions. Physiological effects were assessed in liver and brain using the following biomarkers: activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd), the detoxifying enzyme glutathione S-transferase (GST) and malondialdehyde (MDA) as indicative of lipid peroxidation. Individuals were recorded for behavior analysis (i.e. social interactions and feeding behavior). Results revealed an increase in cellular stress from control to weathered fish groups, with the virgin group showing intermediate levels in all quantified biomarkers. Significant differences were found in the liver for all biomarkers except for MDA, suggesting that exposure time to MPs in this experiment is long enough to trigger the activation of antioxidant enzymes but not to produce cell damage by lipid peroxidation. In brain tissue samples, fish from the weathered group presented significantly higher values for CAT and SOD, highlighting its function as primary antioxidants. Regarding behavioral effects, results showed that the two MPs enriched groups were significantly bolder during social interactions and, although no significantly, tended to be more active during feeding. In conclusion, MPs which have been weathered in marine environmental conditions produces a higher physiological response than virgin MPs but also, a physiological response is variable depending on the tissue analyzed. In addition, a short period to MP exposure seems to affect overall social and feeding behavior but, further research is needed to assess long-term effects of MP ingestion and its potential consequences on fish populations.


Asunto(s)
Conducta Animal , Ingestión de Alimentos , Microplásticos/toxicidad , Dorada/fisiología , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Análisis de Componente Principal , Superóxido Dismutasa/metabolismo , Contaminantes Químicos del Agua/toxicidad
13.
Aquat Toxicol ; 231: 105739, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33434705

RESUMEN

Cadmium (Cd) with no known functional role in any life-form has myriad of harmful effects. The present study was designed to elucidate the mechanism of Cd-induced oxystress generation and its impact on antioxidant and apoptosis signaling pathways in head kidney macrophage (HKM) of Channa punctatus Bloch. Fish were sampled and acclimatized with one group treated with cadmium chloride (CdCl2) (1.96 mg/L) and another as untreated control group, both kept under observation for 7 days. Exposure to Cd caused ultrastructural changes along with reduced head kidney somatic index (HKSI). Significantly increased levels of reactive oxygen species (ROS), respiratory burst activity, lipid peroxidation, DNA fragmentation and superoxide dismutase were found in the HKM from the treated group as compared to control. In contrast, antioxidant enzymes like catalase and reduced glutathione activity decreased in the Cd exposed group. The suppressed antioxidant activity was further confirmed and corroborated from the altered expression of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2) genes, the major player of antioxidant pathway. Cd induced alteration in Nrf2-Keap1 signaling pathway was also validated by the diminished levels of Nrf2 dependent expression of protein like heme oxygenase-1 (HO-1). The flow cytometry analysis supported the event of apoptosis in Cd exposed group as compared to control, which was further confirmed by the upregulated expression of caspase-3, caspase-8, caspase-9, TNF-α and p53 genes from the real-time gene expression study. In addition, altered protein level of cytochrome C validates the incidence of apoptosis. Altogether, our results demonstrate that exposure to Cd caused oxidative stress in HKM of Channa punctatus Bloch. by compromising the antioxidant enzyme activities via the down regulation of expression of genes related to antioxidant signaling pathway besides encouraging apoptosis via both mitochondrial and death receptor pathway.


Asunto(s)
Apoptosis , Cadmio/toxicidad , Peces/metabolismo , Riñón Cefálico/citología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Macrófagos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/ultraestructura , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Receptores de Muerte Celular/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Contaminantes Químicos del Agua/toxicidad
14.
Int J Mol Sci ; 22(2)2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33467472

RESUMEN

Melatonin priming is an effective strategy to improve the germination of aged oat (Avena sativa L.) seeds, but the mechanism involved in its time-course responses has remained largely unknown. In the present study, the phenotypic differences, ultrastructural changes, physiological characteristics, and proteomic profiles were examined in aged and melatonin-primed seed (with 10 µM melatonin treatment for 12, 24, and 36 h). Thus, 36 h priming (T36) had a better remediation effect on aged seeds, reflecting in the improved germinability and seedlings, relatively intact cell ultrastructures, and enhanced antioxidant capacity. Proteomic analysis revealed 201 differentially abundant proteins between aged and T36 seeds, of which 96 were up-accumulated. In melatonin-primed seeds, the restoration of membrane integrity by improved antioxidant capacity, which was affected by the stimulation of jasmonic acid synthesis via up-accumulation of 12-oxo-phytodienoic acid reductase, might be a candidate mechanism. Moreover, the relatively intact ultrastructures enabled amino acid metabolism and phenylpropanoid biosynthesis, which were closely associated with energy generation through intermediates of pyruvate, phosphoenolpyruvate, fumarate, and α-ketoglutarate, thus providing energy, active amino acids, and secondary metabolites necessary for germination improvement of aged seeds. These findings clarify the time-course related pathways associated with melatonin priming on promoting the germination of aged oat seeds.


Asunto(s)
Avena/metabolismo , Germinación/efectos de los fármacos , Melatonina/farmacología , Proteómica/métodos , Semillas/metabolismo , Antioxidantes/metabolismo , Avena/genética , Avena/ultraestructura , Regulación del Desarrollo de la Expresión Génica , Ontología de Genes , Germinación/genética , Peróxido de Hidrógeno/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Melatonina/metabolismo , Microscopía Electrónica de Transmisión , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteoma/genética , Proteoma/metabolismo , Plantones/efectos de los fármacos , Plantones/genética , Plantones/metabolismo , Semillas/genética , Semillas/ultraestructura , Factores de Tiempo
15.
Molecules ; 26(3)2021 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-33513835

RESUMEN

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen's Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Catequina/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Animales , Antioxidantes/fisiología , Benzo(a)pireno/farmacología , Embrión de Pollo , Pollos , Modelos Animales de Enfermedad , Femenino , India , Inflamación/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Ratones , Ratas , Ratas Sprague-Dawley , Ratas Wistar
16.
Life Sci ; 268: 118998, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33417953

RESUMEN

AIM: Hyperuricemia is defined by the European Rheumatology Society as a uric acid level greater than 6 mg/dl (60 mg/l or 360 µmol/l). Our goal was to evaluate the hypouricemic effect of nettle. For this reason, we have first of all try to create an hyperuricemic animal model which is very suitable because at the level of literature there is not an exact model, there are many models and our objective is to set an adequate model. MATERIALS AND METHODS: An attempt has been made to test acute and chronic hyperuricemia by varying the duration and method of induction of potassium oxonate. Similarly, attempts have been made to induce chronic hyperuricemia through an animal and vegetable diet. The reversibility of hyperuricemia was tested with a maintenance protocol. KEY FINDINGS: For the creation of the hyperuricemia model, it has been shown that acute hyperuricemia cannot be induced by short administration of potassium oxonate and persistent chronic hyperuricemia can be induced only after daily administration of oxonate of potassium by intraperitoneal injection for 15 days. Indeed, hyperuricemia was reversible after stopping the administration of potassium oxonate. The high-purine diet is also capable of inducing chronic hyperuricemia but to a less extent. SIGNIFICANCE: After creating an adequate model of hyperuricemia while setting the dose of potassium oxonate, route of administration and duration. A maintenance protocol was followed which subsequently made it possible to deduce that the daily administration of potassium oxonate must be continued to maintain the hyperuricemia.


Asunto(s)
Hiperuricemia/etiología , Hiperuricemia/patología , Ácido Oxónico/toxicidad , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Enfermedad Crónica , Creatinina/sangre , Modelos Animales de Enfermedad , Hiperuricemia/inducido químicamente , Riñón/efectos de los fármacos , Riñón/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratas Wistar , Urea/sangre , Ácido Úrico/sangre
17.
Food Chem ; 346: 128845, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33387832

RESUMEN

The essential oil extracted from the black Piper nigrum L. (BPEO) was analyzed for antioxidant, hepatoprotective and antifungal activities. BPEO is rich in total phenolics, total flavonoids and proanthocyanidins, and showed good free radicals and lipid peroxidation scavenging capacities. In a CCl4-induced liver injury mice model, the BPEO treated groups showed increases in the catalase (CAT), glutathione (GSH) and total superoxide dismutase (T-SOD) activities present in the liver and kidney, and reverses the CCl4-elevated total bilirubin (TBIL), glutamate pyruvate transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) and malondialdehyde (MDA) level, which were confirmed in further analyses of kidney tissue sections. BPEO can effectively inhibit the growth of Aspergillus flavus spoilage fungus in maize. Further analyses indicated that BPEO disrupt the permeability barrier of the cell membrane and lead to mitochondrial dysfunction in A. flavus. Therefore, the current study proved BPEO's potential as hepatoprotective products and natural food preservatives.


Asunto(s)
Antifúngicos/farmacología , Antioxidantes/farmacología , Piper nigrum/metabolismo , Alanina Transaminasa , Animales , Aspartato Aminotransferasas , Tetracloruro de Carbono/toxicidad , Catalasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Flavonoides/farmacología , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Extractos Vegetales/farmacología
18.
Life Sci ; 269: 119027, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33453248

RESUMEN

Identifying miRNAs involved in cancer and devising strategies to control their expression is a new therapeutic approach. Valproic acid (VPA) has attracted a lot of interest in cancer research. We evaluated the impact of VPA on the expression of miR-34a, miR-520h, and their target gene histone deacetylase 1 (HDAC1), as well as their relationship with apoptosis in breast cancer. First, through bioinformatics analyses, the possible target genes of miR-34a and miR-520h and their roles in apoptosis regulation were investigated. Then, miR-34a, miR-520h, and HDAC1 gene expression in tissues of breast cancer patients were determined using the qRT-PCR method. The anticancer impact of VPA on apoptosis and the expression levels of miR-34a, miR-520h, and HDAC1 gene were measured in MCF-7 and MDA-MB-231 cell lines. The bioinformatics analyses indicated that miR-34a and miR-520h might make a unique contribution in regulating the apoptosis pathway. The relative expression of miR-34a and miR-520h significantly decreased in cancer tissues, while the relative expression of HDAC1 increased. In the in vitro study, VPA led to apoptosis induction and increased lipid peroxidation products in breast cancer cells. Moreover, VPA increased the expression of miR- 34a and miR-520h and decreased HDAC1 expression in MCF-7 cells. In MDA-MB-231 cells, VPA decreased the expression of these miRNAs and increased the expression of HDAC1. It can be concluded that miR-34a and miR-520h are implicated in the apoptosis pathways, and thus, VPA can recruit as a possible option in breast cancer research due to its interference with epigenetic processes.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Histona Desacetilasa 1/genética , MicroARNs/genética , Ácido Valproico/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Neoplasias de la Mama/diagnóstico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes , Histona Desacetilasa 1/metabolismo , Humanos , Peroxidación de Lípido/efectos de los fármacos , MicroARNs/metabolismo , Persona de Mediana Edad , Curva ROC , Especies Reactivas de Oxígeno/metabolismo
19.
Ecotoxicol Environ Saf ; 208: 111588, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396111

RESUMEN

Rare earth elements (REEs) have been recently identified as emergent contaminants because of their numerous and increasing applications in technology. The impact of REEs on downstream ecosystems, notably aquatic organisms, is of particular concern, but has to date been largely overlooked. The purpose of this study was thus to evaluate the toxicity of lanthanide metals, lutetium (Lu) and dysprosium (Dy) in rainbow trout after 96 h of exposure. The lethal concentration (LC50) was determined and the expression of 14 genes involved in different pathways such as oxidative stress, xenobiotic detoxification, mitochondrial respiration, DNA repair, protein folding and turnover, inflammation, calcium binding and ammonia metabolism were quantified in surviving fish. In parallel, lipid peroxidation (LPO), DNA damage (DSB), metallothionein level (MT) and cyclooxygenase activity (COX) were examined. The acute 96 h-LC50 data revealed that Lu was more toxic than Dy (1.9 and 11.0 mg/L, respectively) and was able to affect all investigated pathways by changing the expression of the studied genes, to the exception of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). It also induced a decrease in DNA repair at concentrations 29 times below the LC50. This suggests that Lu could trigger a general stress to disrupt the cell homeostasis leading to genotoxicity without promoting oxidative stress. However, Dy induced modulation in the expression of genes involved in the protection against oxidative stress, detoxification, mitochondrial respiration, immunomodulation, protein turnover and an increase in the DNA strand breaks at concentrations 170 times lower than LC50. Changes in mRNA level transcripts could represent an early signal to prevent against toxicity of Dy, which exhibited inflammatory and genotoxic effects. This study thus provides useful knowledge enhancing our understanding of survival strategies developed by rainbow trout to cope with the presence of lanthanides in the environment.


Asunto(s)
Disprosio/toxicidad , Lutecio/toxicidad , Oncorhynchus mykiss/fisiología , Contaminantes Químicos del Agua/toxicidad , Animales , Catalasa/metabolismo , Daño del ADN , Reparación del ADN , Disprosio/metabolismo , Ecosistema , Glutatión Transferasa/metabolismo , Dosificación Letal Mediana , Peroxidación de Lípido/efectos de los fármacos , Lutecio/metabolismo , Metalotioneína/metabolismo , Metales de Tierras Raras , Oncorhynchus mykiss/metabolismo , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismo
20.
Ecotoxicol Environ Saf ; 208: 111601, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33396121

RESUMEN

Atrazine (ATZ) is among the most widely used herbicides in the world, and yet it has a potential to contaminate aquatic environments due to pesticide leaching from agricultural areas. In the Neotropical region, studies about the effects of this herbicide in native aquatic wildlife is scarce.Our study aimed at investigating the effects of a 30-day exposure to a commercial atrazine formulation on oxidative stress parameters, histopathology in testis and liver, and hormone levels in males and female of yellow-tailed tetra fish (Astyanax altiparanae). Adults were exposed to low but environmentally relevant concentrations of atrazine as follows: 0 (CTL-control), 0.5 (ATZ0.5), 1 (ATZ1), 2 (ATZ2) and 10 (ATZ10) µg/L. Our results showed decreased GST activity in gills in all groups of exposed animals and increased CAT activity in gills from the ATZ10 group. In the liver, there was an increase in lipid peroxidation in fish from ATZ1 and ATZ2 groups. Histological analysis of the liver showed increased percentage of sinusoid capillaries in ATZ2 fish, increased vascular congestion in ATZ1 and increased leukocyte infiltration in the ATZ10 group. Hepatocyte diameter analysis revealed a decrease in cell size in all groups exposed to ATZ, and a decrease in hepatocyte nucleus diameter in ATZ1, ATZ2 and ATZ10 groups. Endocrine parameters did not show significant changes following ATZ exposure, although an increase of triiodothyronine/thyroxine (T3/T4) ratio was observed in ATZ2 fish. Our results provide evidence that even low, environmentally relevant concentrations of ATZ produced oxidative damage and histological alterations in adult yellow-tailed tetra.


Asunto(s)
Atrazina/toxicidad , Characidae/metabolismo , Herbicidas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Atrazina/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Branquias/efectos de los fármacos , Branquias/metabolismo , Herbicidas/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Contaminantes Químicos del Agua/metabolismo
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