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1.
Chem Biol Interact ; 339: 109432, 2021 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-33684387

RESUMEN

Mitochondrial dependent oxidative stress (OS) and subsequent cell death are considered as the major cytotoxicity caused by Triethylene glycol dimethacrylate (TEGDMA), a commonly monomer of many resin-based dental composites. Under OS microenvironment, autophagy serves as a cell homeostatic mechanism and maintains redox balance through degradation or turnover of cellular components in order to promote cell survival. However, whether autophagy is involved in the mitochondrial oxidative damage and apoptosis induced by TEGDMA, and the cellular signaling pathways underlying this process remain unclear. In the present study, we demonstrated that TEGDMA induced mouse preodontoblast cell line (mDPC6T) dysfunctional mitochondrial oxidative response. In further exploring the underlying mechanisms, we found that TEGDMA impaired autophagic flux, as evidenced by increased LC3-II expression and hindered p62 degradation, thereby causing both mitochondrial oxidative damage and cell apoptosis. These results were further verified by treatment with chloroquine (autophagy inhibitor) and rapamycin (autophagy promotor). More importantly, we found that the JNK/MAPK pathway was the key upstream regulator of above injury process. Collectively, our finding firstly demonstrated that TEGDMA induced JNK-dependent autophagy, thereby promoting mitochondrial dysfunction-associated oxidative damage and apoptosis in preodontoblast.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Polietilenglicoles/farmacología , Ácidos Polimetacrílicos/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cloroquina/farmacología , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Oxidación-Reducción/efectos de los fármacos , Proteínas de Unión al ARN/metabolismo , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología
2.
J Enzyme Inhib Med Chem ; 36(1): 659-668, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33641565

RESUMEN

Human intestinal epithelial cell line-6 (HIEC-6) cells and primary human hepatocytes (PHHs) were treated with 3-amidinophenylalanine-derived inhibitors of trypsin-like serine proteases for 24 hours. It was proven that treatment with MI-1900 and MI-1907 was tolerated up to 50 µM in HIEC-6. These inhibitors did not cause elevations in extracellular H2O2 levels and in the concentrations of interleukin (IL)-6 and IL-8 and did not alter occludin distribution in HIEC-6. It was also found that MI-1900 and MI-1907 up to 50 µM did not affect cell viability, IL-6 and IL-8 and occludin levels of PHH. Based on our findings, these inhibitors could be safely applicable at 50 µM in HIEC-6 and in PHH; however, redox status was disturbed in case of PHH. Moreover, it has recently been demonstrated that MI-1900 prevents the replication and spread of the new SARS-CoV-2 in infected Calu-3 cells, most-likely via an inhibition of the membrane-bound host protease TMPRSS2.


Asunto(s)
Antivirales/farmacología , Células Epiteliales/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Fenilalanina/farmacología , Inhibidores de Proteasas/farmacología , Serina Endopeptidasas/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Epiteliales/citología , Células Epiteliales/enzimología , Regulación de la Expresión Génica/efectos de los fármacos , Hepatocitos/citología , Hepatocitos/enzimología , Humanos , Peróxido de Hidrógeno/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/enzimología , Ocludina/genética , Ocludina/metabolismo , Oxidación-Reducción/efectos de los fármacos , Fenilalanina/análogos & derivados , Cultivo Primario de Células , Serina Endopeptidasas/genética
3.
Food Chem ; 351: 129272, 2021 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-33639432

RESUMEN

Enzymes and their concentrations are crucial factors in improving the release of nutraceuticals bounded to rice bran's cell wall matrix. This study aims to investigate the optimal concentrations of Viscozyme and Fiberzyme at 3-30 beta-glucanase units/2 g in improving the release of phenolics, tocopherols, tocotrienols, and γ-oryzanol fractions and enhancing the bioactivities of red rice bran. At specific concentrations, Fiberzyme increased ferulic (301%) and caffeic acid (691%) in soluble phenolics, p-coumaric acid (98%), and catechin (161%) in bound phenolics as well as γ-oryzanol fractions(32%-134%) and increased ferric reducing power (90%), DPPH (41%), and hydroxyl (25%) radical scavenging activities. Viscozyme enhanced δ,γ,α-tocopherols (11%-164%) and tocotrienols (39%-271%) and scavenging activities against nitric oxide (144%), superoxide anion (120%), and inhibition of human LDL oxidation (40%). Cycloartenyl ferulate, ferulic acid, soluble phenolics, campesteryl ferulate, 24-methylenecycloartanyl ferulate, and α-tocotrienol showed a significant positive correlation with bioactivities. Thus, optimization of enzymatic processing will help process the red rice bran into a nutraceutical rich ingredient having higher biological activity.


Asunto(s)
Antioxidantes/química , Antioxidantes/farmacología , Fibras de la Dieta/análisis , Suplementos Dietéticos/análisis , Enzimas/metabolismo , Lipoproteínas LDL/metabolismo , Oryza/química , Antioxidantes/metabolismo , Humanos , Oxidación-Reducción/efectos de los fármacos
4.
Oxid Med Cell Longev ; 2021: 6646923, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33628371

RESUMEN

Inflammatory lung disease results in a high global burden of death and disability. There are no effective treatments for the most severe forms of many inflammatory lung diseases, such as chronic obstructive pulmonary disease, emphysema, corticosteroid-resistant asthma, and coronavirus disease 2019; hence, new treatment options are required. Here, we review the role of oxidative imbalance in the development of difficult-to-treat inflammatory lung diseases. The inflammation-induced overproduction of reactive oxygen species (ROS) means that endogenous antioxidants may not be sufficient to prevent oxidative damage, resulting in an oxidative imbalance in the lung. In turn, intracellular signaling events trigger the production of proinflammatory mediators that perpetuate and aggravate the inflammatory response and may lead to tissue damage. The production of high levels of ROS in inflammatory lung diseases can induce the phosphorylation of mitogen-activated protein kinases, the inactivation of phosphoinositide 3-kinase (PI3K) signaling and histone deacetylase 2, a decrease in glucocorticoid binding to its receptor, and thus resistance to glucocorticoid treatment. Hence, antioxidant treatment might be a therapeutic option for inflammatory lung diseases. Preclinical studies have shown that antioxidants (alone or combined with anti-inflammatory drugs) are effective in the treatment of inflammatory lung diseases, although the clinical evidence of efficacy is weaker. Despite the high level of evidence for the efficacy of antioxidants in the treatment of inflammatory lung diseases, the discovery and clinical investigation of safer, more efficacious compounds are now a priority.


Asunto(s)
Antioxidantes/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/metabolismo , Animales , Humanos , Inflamación/inmunología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Enfermedades Pulmonares/inmunología , Oxidación-Reducción/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Especies Reactivas de Oxígeno/metabolismo
5.
Poult Sci ; 100(2): 918-925, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33518145

RESUMEN

Oxidative stress has always been a hot topic in poultry science. However, studies concerning the effects of redox status and glucose metabolism induced by hydrogen peroxide (H2O2) in the breast muscle of broilers have been rarely reported. This study was aimed to evaluate the impact of intraperitoneal injection of H2O2 on oxidative damage and glycolysis metabolism of breast muscle in broilers. We also explored the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to provide possible mechanism of the redox imbalance. Briefly, a total of 320 one-day-old Arbor Acres chicks were randomly divided into 5 treatments with 8 replicates of 8 birds each (noninjected control, 0.75% saline-injected, 2.5, 5.0, and 10.0% H2O2-injected treatments). Saline group was intraperitoneally injected with physiological saline (0.75%) and H2O2 groups received an intraperitoneal injection of H2O2. The dosage of the injection was 1.0 mL/kg BW. All birds in the saline and H2O2 groups were injected on days 16 and 37 of the experimental period. At 42 d of age, 40 birds (8 cages per group and one chicken per cage) were selected to be stunned electrically (50 V, alternating current, 400 Hz for 5 s each one), and then immediately slaughtered via exsanguination. The results showed that broilers in the H2O2 injection group linearly exhibited higher contents of reactive oxygen species, carbonyl and malondialdehyde, and lower total antioxidant capacity and glutathione peroxidase activities. With the content of H2O2 increased, the H2O2 groups linearly downregulated the mRNA expressions of GPX, CAT, HMOX1, NQO1, and Nrf2 and its downstream target genes. In addition, H2O2 increased serum activities of creatine kinase and lactate dehydrogenase. Meanwhile, in the pectoral muscle, the glycogen content was linearly decreased, and the lactate content was linearly increased in muscle of broilers injected with H2O2. In addition, the activities of glycolytic enzymes including pyruvate kinase, hexokinase, and lactate dehydrogenase were linearly increased after exposure to H2O2. In conclusion, H2O2 injection could impair antioxidant status and enhance anaerobic metabolism of breast muscle in broilers.


Asunto(s)
Pollos , Peróxido de Hidrógeno/efectos adversos , Oxidantes/efectos adversos , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Músculos Pectorales/metabolismo , Animales , Antioxidantes/metabolismo , Pollos/metabolismo , Suplementos Dietéticos , Músculos Pectorales/efectos de los fármacos , Distribución Aleatoria
6.
Food Chem ; 349: 129066, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33556728

RESUMEN

The objective of this study was to explore the oxidative modification induced by AAPH (2,2'-azobis (2-amidinopropane) dihydrochloride) on the microbial transglutaminase (MTGase) cross-linking reaction and gelling properties of silver carp myofibril protein (SCMP). Compared to AAPH treatment, MTGase addition resulted further changes of protein properties as evidenced by the decreasing free amino and thiol group content, the decreased secondary and tertiary structure, and the increasing storage modulus (G') and gel strength (P < 0.05). The proper oxidation induced by AAPH (5 mM) promoted the glutamine-lysine and disulfide cross-linking due to MTGase (10 U/g). Therefore, the quality of the SCMP gel was improved with a good water-holding capacity (WHC), gel strength and G'. This results could lay a theoretical foundation for the development of silver carp surimi products with good quality. Chemical compounds: (2,2'-azobis(2-amidinopropane)dihydrochloride (PubChem CID:76344); O-Phthalaldehyde (PubChem CID:4807); 5,5'-Dithiobis(2-Nitrobenzoic Acid) (PubChem CID:6254); 8-Anilino-1-naphthalenesulfonic acid (PubChem CID:1369); Acrylamide (PubChem CID: 6579); ß-Mercaptoethanol (PubChem CID: 1567); Sodium dodecyl sulfate (PubChem CID:3423265).


Asunto(s)
Carpas , Proteínas Musculares/química , Peróxidos/farmacología , Proteínas/metabolismo , Animales , Geles , Oxidación-Reducción/efectos de los fármacos , Alimentos Marinos , Compuestos de Sulfhidrilo/química , Transglutaminasas/metabolismo , Agua/química
7.
Molecules ; 26(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525350

RESUMEN

Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.


Asunto(s)
Cinetina/farmacología , Cinetina/toxicidad , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/toxicidad , Animales , Antioxidantes/fisiología , Antioxidantes/toxicidad , Biomarcadores/metabolismo , Creatinina/metabolismo , Citocininas/metabolismo , Glucosa/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/metabolismo , Túbulos Renales/efectos de los fármacos , Túbulos Renales/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/toxicidad , Ratas , Receptores Purinérgicos P1/metabolismo
8.
Molecules ; 26(4)2021 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-33562280

RESUMEN

Oxidative protein folding is a biological process to obtain a native conformation of a protein through disulfide-bond formation between cysteine residues. In a cell, disulfide-catalysts such as protein disulfide isomerase promote the oxidative protein folding. Inspired by the active sites of the disulfide-catalysts, synthetic redox-active thiol compounds have been developed, which have shown significant promotion of the folding processes. In our previous study, coupling effects of a thiol group and guanidyl unit on the folding promotion were reported. Herein, we investigated the influences of a spacer between the thiol group and guanidyl unit. A conjugate between thiol and guanidyl units with a diethylene glycol spacer (GdnDEG-SH) showed lower folding promotion effect compared to the thiol-guanidyl conjugate without the spacer (GdnSH). Lower acidity and a more reductive property of the thiol group of GdnDEG-SH compared to those of GdnSH likely resulted in the reduced efficiency of the folding promotion. Thus, the spacer between the thiol and guanidyl groups is critical for the promotion of oxidative protein folding.


Asunto(s)
Glicol de Etileno/química , Estrés Oxidativo/efectos de los fármacos , Proteína Disulfuro Isomerasas/química , Compuestos de Sulfhidrilo/química , Catálisis , Cisteína/química , Disulfuros/química , Glicol de Etileno/farmacología , Glutatión/química , Cinética , Oxidación-Reducción/efectos de los fármacos , Pliegue de Proteína/efectos de los fármacos , Compuestos de Sulfhidrilo/farmacología
9.
Int J Mol Sci ; 22(2)2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33430449

RESUMEN

Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α1- and ß1-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α1- and ß1-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α1- and ß1-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.


Asunto(s)
Inflamación/genética , Óxido Nítrico/genética , Periodoncio/metabolismo , Guanilil Ciclasa Soluble/genética , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , GMP Cíclico/genética , Regulación de la Expresión Génica/genética , Hemo/genética , Humanos , Inflamación/patología , Hierro/metabolismo , Osteoclastos/metabolismo , Oxidación-Reducción/efectos de los fármacos , Ligamento Periodontal/metabolismo , Ligamento Periodontal/patología , Periodoncio/patología
10.
Int J Biol Macromol ; 170: 532-539, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33388321

RESUMEN

Seaweed lectins are very promising biotechnological tools that also gain prominence when applied to the pharmacology field. The purpose of the present work was to isolate and characterize lectin from the red algae Amansia multifida and subsequently test it in general inflammation models. The lectin was purified by ion exchange chromatography, characterized with two-dimensional electrophoresis, automated analysis of amino acid sequences and circular dichroism spectroscopy. The pharmacological tests performed were paw edema induced by carrageenan or rapid inflammatory mediators, peritonitis induced by carrageenan and myeloperoxidase leukocyte count assays, glutathione and cytokine concentration. Our results have identified a 30 KDa molecular weight protein that presents a major secondary structure arranged in ß-strand elements (~43%). A fragment of 20 amino acid residues was sequenced and presented low identity to the known classes of lectins from marine alga. This lectin was able to modulate inflammatory parameters such as paw edema, leukocyte migration, oxidative stress and proinflammatory cytokines. Thus, the lectin from the seaweed Amansia multifida has evident anti-inflammatory properties because it acts by reducing the formation of edema by modulating the effect of vascular mediators, migration of neutrophils, proinflammatory cytokines and oxidative stress control.


Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Lectinas/química , Lectinas/farmacología , Rhodophyta/química , Animales , Carragenina/farmacología , Movimiento Celular/efectos de los fármacos , Citocinas/metabolismo , Edema/tratamiento farmacológico , Edema/metabolismo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/química , Mediadores de Inflamación/farmacología , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Ratones , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Peritonitis/tratamiento farmacológico , Peritonitis/metabolismo , Peroxidasa/metabolismo
11.
Nat Commun ; 12(1): 26, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397915

RESUMEN

Mitochondrial oxidation-induced cell death, a physiological process triggered by various cancer therapeutics to induce oxidative stress on tumours, has been challenging to investigate owing to the difficulties in generating mitochondria-specific oxidative stress and monitoring mitochondrial responses simultaneously. Accordingly, to the best of our knowledge, the relationship between mitochondrial protein oxidation via oxidative stress and the subsequent cell death-related biological phenomena has not been defined. Here, we developed a multifunctional iridium(III) photosensitiser, Ir-OA, capable of inducing substantial mitochondrial oxidative stress and monitoring the corresponding change in viscosity, polarity, and morphology. Photoactivation of Ir-OA triggers chemical modifications in mitochondrial protein-crosslinking and oxidation (i.e., oxidative phosphorylation complexes and channel and translocase proteins), leading to microenvironment changes, such as increased microviscosity and depolarisation. These changes are strongly related to cell death by inducing mitochondrial swelling with excessive fission and fusion. We suggest a potential mechanism from mitochondrial oxidative stress to cell death based on proteomic analyses and phenomenological observations.


Asunto(s)
Iridio/farmacología , Mitocondrias/metabolismo , Fármacos Fotosensibilizantes/farmacología , Muerte Celular/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Transferencia de Energía , Células HEK293 , Células HeLa , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Proteínas Mitocondriales/metabolismo , Oxidación-Reducción/efectos de los fármacos , Proteoma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Viscosidad
12.
Chem Biol Interact ; 335: 109367, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33412154

RESUMEN

Metastasis is the leading cause of death in retinoblastoma (Rb) patients. Tubeimoside II (TBMS II) is a compound enriched in the Traditional Chinese Medicine (TCM) Tu Bei Mu. It has been shown to induce cytotoxicity of several types of tumors; however, littler is known about its effect on Rb. This study investigated the influence of TBMS II on TGF-ß1-induced metastasis of human retinoblastoma Y-79 and WERI-Rb-1 cells. The data showed that TBMS II significantly inhibited epithelial-mesenchymal transition (EMT), cell adhesion, migration and invasion via reducing TGF-ß1-induced oxidative stress in Rb cells. Further findings revealed that TBMS II exerted its inhibitory effect against TGF-ß1-induced metastatic progression of Rb cells via suppressing redoxosome-dependent EGFR activation including EGFR phosphorylation and oxidation, and the activation of such signaling attenuated TBMS II's effect. Our study reveals that TBMS II impacts on TGF-ß1-induced metastatic progression of Rb cells, and this information may contribute to better understanding the therapeutic potentials of TBMS II on metastatic Rb.


Asunto(s)
Antineoplásicos/farmacología , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Saponinas/farmacología , Triterpenos/farmacología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Transición Epitelial-Mesenquimal/efectos de los fármacos , Receptores ErbB/metabolismo , Humanos , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
13.
Life Sci ; 267: 118945, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33359745

RESUMEN

AIMS: Oxidized phospholipids (OxPLs) are formed as a result of oxidative stress, which potentially mediate multiple pathological effects. We aimed to evaluate the effects of hydrogen (H2) on OxPLs in vivo and the underlying mechanism. MAIN METHODS: Rats were randomly assigned to three groups: control group fed with a chow diet, model group fed with a high-fat diet, and H2-treated group fed with a high-fat diet and treated by 4% H2 inhalation for ten weeks. OxPLs in liver and plasma were analyzed by liquid chromatography-mass spectrometry. High-density lipoprotein (HDL) was separated by ultracentrifugation. A proteomic analysis was performed to reveal the alternation of HDL protein composition and he antioxidant capacity of HDL was tested by low-density lipoprotein oxidation experiment. Furthermore, the activity or expression of HDL-associated enzymes were evaluated. KEY FINDINGS: Inhalation of 4% H2 decreased the accumulation of OxPLs in rats. In vitro tests revealed that the different concentrations of H2 did not inhibit the formation of OxPLs mediated by non-enzymatic oxidation. H2 inhalation altered the components and enhanced the anti-oxidative capacity of HDL in rats fed with a high-fat diet. Further experiments showed that H2 significantly regulated the activity of lipoprotein-associated phospholipase A2, paraoxonase-1, and the expression of lecithin:cholesterol acyltransferase. SIGNIFICANCE: Our findings revealed that H2 may reduce the OxPLs levels through its influence on HDL-associated enzymes that can act on OxPLs, suggesting that H2 can be used in alleviating diseases related to lipid peroxidation due to oxidative stress.


Asunto(s)
Hidrógeno/metabolismo , Hidrógeno/farmacología , Fosfolípidos/metabolismo , Administración por Inhalación , Animales , Antioxidantes/farmacología , Apolipoproteína A-I/metabolismo , HDL-Colesterol/efectos de los fármacos , HDL-Colesterol/metabolismo , Cromatografía Liquida/métodos , Dieta Alta en Grasa/efectos adversos , Peroxidación de Lípido , Lipoproteínas HDL/efectos de los fármacos , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Hígado/metabolismo , Masculino , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosfatidilcolina-Esterol O-Aciltransferasa/metabolismo , Proteómica/métodos , Ratas , Ratas Sprague-Dawley
14.
Biochim Biophys Acta Gen Subj ; 1865(1): 129768, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33148501

RESUMEN

BACKGROUND: Extensive research is being carried out globally to design and develop new selenium compounds for various biological applications such as antioxidants, radio-protectors, anti-carcinogenic agents, biocides, etc. In this pursuit, 3,3'-diselenodipropionic acid (DSePA), a synthetic organoselenium compound, has received considerable attention for its biological activities. SCOPE OF REVIEW: This review intends to give a comprehensive account of research on DSePA so as to facilitate further research activities on this organoselenium compound and to realize its full potential in different areas of biological and pharmacological sciences. MAJOR CONCLUSIONS: It is an interesting diselenide structurally related to selenocystine. It shows moderate glutathione peroxidase (GPx)-like activity and is an excellent scavenger of reactive oxygen species (ROS). Exposure to radiation, as envisaged during radiation therapy, has been associated with normal tissue side effects and also with the decrease in selenium levels in the body. In vitro and in vivo evaluation of DSePA has confirmed its ability to reduce radiation induced side effects into normal tissues. Administration of DSePA through intraperitoneal (IP) or oral route to mice in a dose range of 2 to 2.5 mg/kg body weight has shown survival advantage against whole body irradiation and a significant protection to lung tissue against thoracic irradiation. Pharmacokinetic profiling of DSePA suggests its maximum absorption in the lung. GENERAL SIGNIFICANCE: Research work on DSePA reported in fifteen years or so indicates that it is a promising multifunctional organoselenium compound exhibiting many important activities of biological relevance apart from radioprotection.


Asunto(s)
Antioxidantes/farmacología , Propionatos/farmacología , Protectores contra Radiación/farmacología , Compuestos de Selenio/farmacología , Animales , Antioxidantes/síntesis química , Antioxidantes/farmacocinética , Antioxidantes/toxicidad , Humanos , Oxidación-Reducción/efectos de los fármacos , Propionatos/síntesis química , Propionatos/farmacocinética , Propionatos/toxicidad , Protectores contra Radiación/síntesis química , Protectores contra Radiación/farmacocinética , Protectores contra Radiación/toxicidad , Especies Reactivas de Oxígeno/metabolismo , S-Nitrosotioles/metabolismo , Compuestos de Selenio/síntesis química , Compuestos de Selenio/farmacocinética , Compuestos de Selenio/toxicidad
15.
Methods Mol Biol ; 2202: 111-124, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32857351

RESUMEN

Different experimental conditions can be used to detect the presence of reactive oxygen species (ROS) in the photodynamic inactivation of microorganisms. Here, we describe the effect of the media and the addition of ROS scavengers to obtain insight about the oxidative processes that take place during the photokilling of bacteria. In addition, 9,10-dimethylanthracene was used to sense the generation of singlet molecular oxygen, O2(1Δg), in microbial cells. Thus, the contribution of type I or type II pathways in the photocytotoxicity action can be rapidly detected and compared between different photosensitizers.


Asunto(s)
Especies Reactivas de Oxígeno/análisis , Oxígeno Singlete/análisis , Oxígeno Singlete/metabolismo , Antracenos/química , Bacterias/metabolismo , Medios de Cultivo/química , Luz , Oxidación-Reducción/efectos de los fármacos , Oxígeno/metabolismo , Fármacos Fotosensibilizantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo
16.
Methods Mol Biol ; 2202: 125-135, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32857352

RESUMEN

Reactive oxygen species (ROS) production within biofilms is studied with a simple and easy setup based on fluorescence microscopy. Herein, a biofilm is exposed to different ROS inducers: a bactericidal antibiotic (ciprofloxacin) and a BODIPY-based photosensitizer (I2B-OAc). Real-time ROS induction in the core of the biofilms is monitored utilizing two fluorescent reporters-AMDA and H2DCFDA-the first one with selectivity toward singlet oxygen (1O2) and the latest for other ROS (O2•-, H2O2, and OH•-). A point-by-point methodology is reported, starting with the sample preparation all the way through the microscope setup and, finally, processing of the images.


Asunto(s)
Microscopía Fluorescente/métodos , Especies Reactivas de Oxígeno/análisis , Oxígeno Singlete/análisis , Antibacterianos/farmacología , Bacterias/metabolismo , Biopelículas/efectos de los fármacos , Compuestos de Boro/farmacología , Ciprofloxacino/farmacología , Peróxido de Hidrógeno , Oxidación-Reducción/efectos de los fármacos , Oxígeno/metabolismo , Fármacos Fotosensibilizantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Oxígeno Singlete/metabolismo
17.
Carbohydr Polym ; 252: 117210, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33183643

RESUMEN

In this study, protocatechuic acid (PCA) was grafted onto carboxymethyl chitosan (CMCS) via EDC/NHS to improve the antioxidant effect. The grafting ratio of PCA-g-CMCS conjugates could be controlled by adjusting the pH value and feed ratio of raw materials. The conjugates exhibited similar pH sensitivity to CMCS and showed dramatic enhancements of DPPH and ABTS radicals scavenging activities, total antioxidant capacity, reducing power, and Fe2+-chelating activity. Three-dimensional porous PCA-g-CMCS hydrogel was prepared by lyophilization and secondary cross-linking. The shaped hydrogel preserved its antioxidant activity, and the sustained release of PCA-containing degraded fragment from biodegradable hydrogel could be achieved with the aid of lysozyme in vitro (15 days). PCA-g-CMCS hydrogel also showed excellent biocompatibility and protective effect on H2O2-induced oxidative damage in SH-SY5Y cells. These results suggested that PCA-g-CMCS conjugates and its hydrogel would appear to be a promising oxidation-resistant material for applications such as drug release and tissue engineering.


Asunto(s)
Antioxidantes , Materiales Biocompatibles/química , Quitosano/análogos & derivados , Hidrogeles/química , Hidroxibenzoatos/química , Fármacos Neuroprotectores , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Línea Celular , Quitosano/química , Humanos , Fenómenos Mecánicos , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Oxidación-Reducción/efectos de los fármacos
18.
J Agric Food Chem ; 69(1): 198-211, 2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33350821

RESUMEN

We explored the effects of dietary supplementation with phlorizin on redox state-related gut microbiota homeostasis in an obesity mouse model. Mice (C57BL/6J) were grouped as follows for 12 weeks: normal chow diet group (NCD), high-fat and cholesterol diet group (HFD), and treatment groups fed with HFD along with three levels of phlorizin. Phlorizin alleviated the hyperlipidemia and redox status and increased the total ccal SCFA content (1.88 ± 0.25 mg/g). Additionally, phlorizin regulated gene expression related to lipid metabolism, redox status, and cecum barrier and rebuilt gut microbiota homeostasis. After interference by antibiotics, the total phloretin content in the feces was decreased about 4-fold, and most of the health-promoting effects were abolished, indicating that phlorizin might be susceptible to microbial biotransformation and that microecology is indispensable for maintaining the redox state capacities of phlorizin. Phlorizin treatment could be an advantageous option for improving HFD-related obesity and redox states related to gut microbiota homeostasis.


Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Malus/química , Obesidad/tratamiento farmacológico , Florizina/administración & dosificación , Extractos Vegetales/administración & dosificación , Animales , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos/análisis , Homeostasis , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/metabolismo , Obesidad/microbiología , Oxidación-Reducción/efectos de los fármacos
19.
Food Chem ; 335: 127647, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32739816

RESUMEN

The inhibition mechanism of the texture deterioration of tilapia fillets after treatment with polyphenols during partial freezing for 49 days was studied. Carnosic acid (CA), procyanidin (PA), quercetin (QE), and resveratrol (RSV) treatments had significantly higher hardness values (over 230 g) than the control group (183 g) on day 49 (P < 0.05). Polyphenol treatments were effective in delaying the protein degradation, lipid oxidation and spoilage microbe growth. Moreover, the kinetic model showed that the predicted shelf life of tilapia fillets treated with PA (102 d) was extended by 25 d compared to the control group (77 d). It was the proposed possible mechanism that polyphenols comprehensively maintained the protein conformation (increased hydrogen bonds and decreased disulfide bonds) and retarded protein denaturation and degradation, protecting the texture of the fillets. Therefore, polyphenols can be used to maintain texture and extend the shelf life of tilapia fillets during partial freezing.


Asunto(s)
Conservación de Alimentos/métodos , Conservantes de Alimentos/farmacología , Carne/análisis , Polifenoles/análisis , Polifenoles/farmacología , Animales , Biflavonoides/química , Catequina/química , Proteínas de Peces/química , Conservación de Alimentos/instrumentación , Congelación , Oxidación-Reducción/efectos de los fármacos , Proantocianidinas/química , Desnaturalización Proteica/efectos de los fármacos , Tilapia
20.
Redox Biol ; 38: 101810, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33360293

RESUMEN

The recent global pandemic due to COVID-19 is caused by a type of coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite rigorous efforts worldwide to control the spread and human to human transmission of this virus, incidence and death due to COVID-19 continue to rise. Several drugs have been tested for treatment of COVID-19, including hydroxychloroquine. While a number of studies have shown that hydroxychloroquine can prolong QT interval, potentially increasing risk of ventricular arrhythmias and Torsade de Pointes, its effects on immune cell function have not been extensively examined. In the current review, an overview of coronaviruses, viral entry and pathogenicity, immunity upon coronavirus infection, and current therapy options for COVID-19 are briefly discussed. Further based on preclinical studies, we provide evidences that i) hydroxychloroquine impairs autophagy, which leads to accumulation of damaged/oxidized cytoplasmic constituents and interferes with cellular homeostasis, ii) this impaired autophagy in part reduces antigen processing and presentation to immune cells and iii) inhibition of endosome-lysosome system acidification by hydroxychloroquine not only impairs the phagocytosis process, but also potentially alters pulmonary surfactant in the lungs. Therefore, it is likely that hydroxychloroquine treatment may in fact impair host immunity in response to SARS-CoV-2, especially in elderly patients or those with co-morbidities. Further, this review provides a rationale for developing and selecting antiviral drugs and includes a brief review of traditional strategies combined with new drugs to combat COVID-19.


Asunto(s)
Presentación de Antígeno/efectos de los fármacos , Antivirales , Muerte Celular Autofágica , Hidroxicloroquina , Pandemias , /inmunología , Antivirales/efectos adversos , Antivirales/uso terapéutico , Muerte Celular Autofágica/efectos de los fármacos , Muerte Celular Autofágica/inmunología , /epidemiología , /patología , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Oxidación-Reducción/efectos de los fármacos
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