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1.
ACS Appl Mater Interfaces ; 13(41): 48433-48448, 2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-34613687

RESUMEN

The excessive colonization of Propionibacterium acnes (P. acnes) is responsible for the genesis of acne vulgaris, a common inflammatory disease of skin. However, the conventional anti-acne therapies are always limited by various side effects, drug resistance, and poor skin permeability. Microneedles (MNs) are emerging topical drug delivery systems capable of noninvasively breaking through the skin stratum corneum barrier to efficiently enhance the transdermal drug penetration. Herein, MNs loaded with intelligent pH-sensitive nanoplatforms were constructed for amplified chemo-photodynamic therapy against acne vulgaris, jointly exerting antimicrobial and anti-inflammatory effects. The photosensitizer indocyanine green (ICG) was loaded into the zeolitic imidazolate framework-8 (ZIF-8) to improve its photostability, which would be triggered by 808 nm laser irradiation to generate cytotoxic reactive oxygen species (ROS) to result in oxidative damage and disturbed metabolic activities of P. acnes. In addition to the efficient drug delivery, the ZIF-8 carrier could selectively degrade in response to the acidic microenvironment of acne lesions, and the released Zn2+ also exhibited a potent antimicrobial activity. The fabricated ZIF-8-ICG@MNs presented an outstanding synergistic anti-acne efficiency both in vitro and in vivo. This bioresponsive microneedle patch is expected to be readily adapted as a generalized, modular strategy for noninvasive therapeutics delivery against superficial skin diseases.


Asunto(s)
Acné Vulgar/tratamiento farmacológico , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Imidazoles/uso terapéutico , Verde de Indocianina/uso terapéutico , Estructuras Metalorgánicas/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Acné Vulgar/patología , Animales , Antibacterianos/química , Antibacterianos/efectos de la radiación , Antibacterianos/toxicidad , Antiinflamatorios/química , Antiinflamatorios/efectos de la radiación , Antiinflamatorios/toxicidad , Células HEK293 , Humanos , Imidazoles/química , Imidazoles/efectos de la radiación , Imidazoles/toxicidad , Verde de Indocianina/química , Verde de Indocianina/efectos de la radiación , Verde de Indocianina/toxicidad , Rayos Infrarrojos , Masculino , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/efectos de la radiación , Estructuras Metalorgánicas/toxicidad , Ratones Endogámicos BALB C , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/efectos de la radiación , Fármacos Fotosensibilizantes/toxicidad , Propionibacterium acnes/efectos de los fármacos , Ratas , Piel/efectos de los fármacos , Piel/patología , Porcinos , Zinc/química , Zinc/efectos de la radiación , Zinc/uso terapéutico , Zinc/toxicidad
2.
ACS Appl Mater Interfaces ; 13(36): 42396-42410, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34472332

RESUMEN

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.


Asunto(s)
Antiinflamatorios/uso terapéutico , Estructuras Metalorgánicas/uso terapéutico , Donantes de Óxido Nítrico/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Antiinflamatorios/efectos de la radiación , Antiinflamatorios/toxicidad , Línea Celular , Escherichia coli/efectos de los fármacos , Luz , Estructuras Metalorgánicas/efectos de la radiación , Estructuras Metalorgánicas/toxicidad , Ratones Endogámicos BALB C , Donantes de Óxido Nítrico/efectos de la radiación , Donantes de Óxido Nítrico/toxicidad , Fármacos Fotosensibilizantes/efectos de la radiación , Fármacos Fotosensibilizantes/toxicidad , Porfirinas/efectos de la radiación , Porfirinas/uso terapéutico , Porfirinas/toxicidad , Staphylococcus aureus/efectos de los fármacos
3.
Food Chem Toxicol ; 152: 112157, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33789119

RESUMEN

The study aimed to study the effects on structural characteristics and anti-inflammatory activities of algal sulfated polysaccharides isolated from Gracilaria lemaneiformis (GLP) after a combined treatment of UV irradiation (average irradiance of 6500 mJ/cm2) and H2O2 (50 mmol/L) for various time periods up to 60 min. After a 30-min treatment, the molecular weight and particle size of GLP was decreased by 15 and 2.6 fold, respectively with small but significant decrease in the contents of total sugars, uronic acids and proteins. There seemed to have no starch and the presence of longer side chains of branches in the GLP samples before and after UV/H2O2 treatment based on the I2-KI assay. Scanning electron microscope and atomic force microscope analysis confirmed that the UV/H2O2 treatment could modify the surface morphology of GLP. GLP treated for 5 min possessed the strongest in vitro anti-inflammatory activity by inhibiting the production of nitric oxide, tumor necrosis factor-α and interleukin-6 by 60.49%, 62.81% and 36.29%, respectively in IEC-6 cells when compared to the model. Therefore, UV/H2O2 treatment had the potential to enhance the anti-inflammatory activity of algal sulfated polysaccharides.


Asunto(s)
Antiinflamatorios/farmacología , Gracilaria/química , Polisacáridos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/efectos de la radiación , Línea Celular , Peróxido de Hidrógeno/química , Interleucina-6/metabolismo , Peso Molecular , Óxido Nítrico/metabolismo , Tamaño de la Partícula , Fotólisis , Polisacáridos/química , Polisacáridos/efectos de la radiación , Ratas , Factor de Necrosis Tumoral alfa/metabolismo , Rayos Ultravioleta , Viscosidad
4.
Chem Commun (Camb) ; 56(31): 4300-4303, 2020 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-32186557

RESUMEN

Reaction of Fe(CO)4Br2 with 2-aminopyridine and 2-aminonapthalene yields ferracyclic iron(ii) complexes bearing two CO ligands. Irradiation with visible light releases these two CO molecules. Substitution of a halide in the parent complexes by thioglucose provides significantly enhanced water solublity and raises the quantum yield for CO release by around five times. The complexes show anti-inflammatory activity in a TNF assay in the dark.


Asunto(s)
Antiinflamatorios/farmacología , Complejos de Coordinación/farmacología , Animales , Antiinflamatorios/efectos de la radiación , Monóxido de Carbono/metabolismo , Complejos de Coordinación/efectos de la radiación , Caballos , Humanos , Hierro/química , Luz , Lipopolisacáridos/farmacología , Mioglobina/metabolismo , Células THP-1 , Factor de Necrosis Tumoral alfa/metabolismo
5.
Am J Phys Med Rehabil ; 99(1): 19-25, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31335343

RESUMEN

OBJECTIVE: The aim of this study was to analyze the effects of low-intensity pulsed ultrasound therapy under different pulse regimes on cultures of semiconfluent L929 fibroblasts, evaluating cell viability, anatomical structural alterations, modulation of vascular endothelial growth factor, interleukin 6, collagen type 1 alpha 1, collagen type 1 alpha 2, and fibroblast growth factor 7, as well as the amount of inflammatory mediators interleukin 2, interleukin 4, interleukin 6, interferon γ, tumor necrosis factor, interleukin 17A, and interleukin 10 at 24, 48, and 72 hrs. DESIGN: The design was experimental study. METHODS: The treatments consisted of 0.2 W/cm doses at a frequency of 1 MHz, with a pulse rate of 10% and 20%. Viability was assessed by the MTT assay (3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide), gene expression by real-time quantitative polymerase chain reaction, and cytokine quantification by flow cytometry. RESULTS: At 48 hrs, ultrasound enhanced cell viability and affected interleukin 6 cytokine production, vascular endothelial growth factor, interleukin 6, type 1 alpha 1 and alpha 2 collagens, and fibroblast growth factor 7 gene modulation. CONCLUSIONS: Low-intensity pulsed ultrasound therapy had a biostimulatory effect on semiconfluent in vitro L929 fibroblast cells, where the group with a dose of 0.2 W/cm-10% (G2) presented higher responses, in all the analyzed aspects, toward the dose pulsed to 20%, confirming its therapeutic properties related to the initial phases of tissue healing.


Asunto(s)
Antiinflamatorios/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Fibroblastos/efectos de la radiación , Terapia por Ultrasonido/métodos , Ondas Ultrasónicas , Células Cultivadas , Colágeno Tipo I/efectos de la radiación , Citocinas/efectos de la radiación , Factor 7 de Crecimiento de Fibroblastos/efectos de la radiación , Humanos , Mediadores de Inflamación/efectos de la radiación , Interleucina-6/efectos de la radiación , Factor A de Crecimiento Endotelial Vascular/efectos de la radiación
6.
Int Immunopharmacol ; 78: 106072, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31835082

RESUMEN

Although the novel resveratrol derivative RM has therapeutic potential for the treatment of inflammatory bowel disease, little is currently known regarding the manner whereby RM regulates excessive inflammatory responses. In this study, we initially investigated the molecular mechanisms underlying the anti-inflammatory effects induced by RM in Toll-like receptor (TLR)-activated macrophages. Upon stimulation with lipopolysaccharide, we found that RM-treated activated macrophages down-regulated the increase in pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-12p70), nitric oxide (NO) production, and activating interleukin-1 receptor-associated kinase 1 (IRAK-1) phosphorylation, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Interestingly, the TLR negative regulator Toll-interacting protein (Tollip) was selectively enhanced during RM stimulation in time- and dose-dependent manners. In response to knockdown of Tollip expression by RNA interference, RM-treated activated macrophages showed augmented expression of inflammatory mediators (pro-inflammatory cytokines, NO, inducible nitric oxidase, and cyclooxygenase-2, and surface molecules) and restored the expression of MAPK and NF-κB signals inhibited by RM treatment. Taken together, our findings indicate that RM has therapeutic potential for treating TLR-induced inflammatory diseases via the promotion of Tollip expression.


Asunto(s)
Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Macrófagos/efectos de los fármacos , Resveratrol/farmacología , Animales , Antiinflamatorios/efectos de la radiación , Antiinflamatorios/uso terapéutico , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Rayos gamma , Técnicas de Silenciamiento del Gen , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/inmunología , Lipopolisacáridos/inmunología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Cultivo Primario de Células , Células RAW 264.7 , Resveratrol/análogos & derivados , Resveratrol/efectos de la radiación , Resveratrol/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Receptores Toll-Like/metabolismo , Regulación hacia Arriba
7.
ChemMedChem ; 13(22): 2408-2414, 2018 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-30203922

RESUMEN

Three new gold(I)-coumarin-based trackable therapeutic complexes and two non-trackable analogues have been synthesised and fully characterised. They all display anti-proliferative properties on several types of cancer cell lines, including those of colon, breast, and prostate. Two complexes displayed significant anti-inflammatory effects; one displayed pro-inflammatory behaviour; this highlights the impact of the position of the fluorophore on the caffeine scaffold. Additionally, the three coumarin derivatives could be visualised in vitro by two-photon microscopy.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Cafeína/análogos & derivados , Cafeína/farmacología , Complejos de Coordinación/farmacología , Cumarinas/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antiinflamatorios/efectos de la radiación , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Cafeína/síntesis química , Cafeína/efectos de la radiación , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Complejos de Coordinación/efectos de la radiación , Cumarinas/síntesis química , Cumarinas/química , Cumarinas/efectos de la radiación , Fluorescencia , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Colorantes Fluorescentes/efectos de la radiación , Oro/química , Células HEK293 , Humanos , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Rayos Ultravioleta
8.
Chemosphere ; 212: 56-66, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30138856

RESUMEN

Prednisolone (PDNN) as an emergent micropollutant directly influences the regional ecological security. In this study, the degradation of PDNN by ultraviolet activated chlorine (UV/chlorine) oxidation process was comprehensively evaluated. The quenching experiment suggested that the PDNN degradation in UV/chlorine process was involved in the participation of hydroxyl radical (OH) and reactive chlorine species (RCS). Influence factors including chlorine dosage, pH, common anion and cation, fulvic acid (FA) on PDNN degradation via UV/chlorine process were investigated. A low chlorine (≤7.1 mg L-1) promoted the PDNN degradation, while a high chlorine dosage (>7.1 mg L-1) was adverse. The pH (4.0-10.0) showed negligible effect, while the investigated anions (Cl-, Br-, HCO3- and SO42-), NH4+ and FA exerted negative impact on PDNN degradation. An efficient process to minimize pharmaceutical micropollutants was the disposal of human urine containing a high concentration of pharmaceutical and potential toxic metabolites. An inhibitory effect was observed in the synthetic urine (fresh urine and hydrolyzed urine). The intermediates/products were identified and the mechanism of PDNN degradation was proposed. PDNN gone through three degradation routes, involving the direct addition of α, ß-unsaturated ketone at C1 or C5, the photolysis of C17 and H-abstraction of C11. The main reactive sites were further determined by comparison of the frontier orbitals calculation and the proposed mechanism. Based on the toxicological tests for PDNN degradation, TP396 (TP396-C1Cl and TP396-C5Cl) and TP414-2-1 (TP414-C1ClC5OH) exhibited much higher toxicity than PDNN, and prolonging reaction time was necessary to achieve PDNN detoxification.


Asunto(s)
Aliivibrio fischeri/efectos de los fármacos , Cloro/química , Prednisolona/metabolismo , Rayos Ultravioleta , Contaminantes Químicos del Agua/orina , Purificación del Agua/métodos , Antiinflamatorios/metabolismo , Antiinflamatorios/efectos de la radiación , Antiinflamatorios/toxicidad , Humanos , Radical Hidroxilo/química , Cinética , Oxidación-Reducción , Fotólisis , Prednisolona/efectos de la radiación , Prednisolona/toxicidad , Pruebas de Toxicidad Aguda
9.
J Am Chem Soc ; 140(30): 9721-9729, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29983046

RESUMEN

The delivery of controlled amounts of carbon monoxide (CO) to biological targets is of significant current interest. Very few CO-releasing compounds are currently known that can be rigorously controlled in terms of the location and amount of CO released. To address this deficiency, we report herein a new metal-free, visible-light-induced CO-releasing molecule (photoCORM) and its prodrug oxidized form, which offer new approaches to controlled, localized CO delivery. The new photoCORM, based on a 3-hydroxybenzo[ g]quinolone framework, releases 1 equiv of CO upon visible-light illumination under a variety of biologically relevant conditions. This nontoxic compound can be tracked prior to CO release using fluorescence microscopy and produces a nontoxic byproduct following CO release. An oxidized prodrug form of the photoCORM is reduced by cellular thiols, providing an approach toward activation in the reducing environment of cancer cells. Strong noncovalent affinity of the nonmetal photoCORM to albumin enables use of an albumin:photoCORM complex for targeted CO delivery to cancer cells. This approach produced cytotoxicity IC50 values among the lowest reported to date for CO delivery to cancer cells by a photoCORM. This albumin:photoCORM complex is also the first CO delivery system to produce significant anti-inflammatory effects when introduced at nanomolar photoCORM concentration.


Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Profármacos/farmacología , Quinolonas/farmacología , Células A549 , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/efectos de la radiación , Antiinflamatorios/toxicidad , Antineoplásicos/metabolismo , Antineoplásicos/efectos de la radiación , Antineoplásicos/toxicidad , Monóxido de Carbono , Bovinos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Luz , Ratones , Profármacos/metabolismo , Profármacos/efectos de la radiación , Profármacos/toxicidad , Unión Proteica , Quinolonas/metabolismo , Quinolonas/efectos de la radiación , Quinolonas/toxicidad , Células RAW 264.7 , Albúmina Sérica Bovina/metabolismo
10.
PLoS One ; 12(7): e0182011, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28759638

RESUMEN

The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs.


Asunto(s)
Antiinflamatorios/efectos de la radiación , Ácido Flufenámico/efectos de la radiación , Ácido Mefenámico/efectos de la radiación , Microondas , Antiinflamatorios/química , Ácido Flufenámico/química , Ácido Mefenámico/química , Solubilidad
12.
Int Immunopharmacol ; 25(2): 249-59, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25701505

RESUMEN

Resveratrol was irradiated at various doses of 15, 30, 50, and 70kGy for the development of physiological functionalities through modification of the structural properties. Gamma irradiation induced a decrease in the resveratrol peak, and the appearance of several new peaks by gamma irradiation was gradually increased up to 70kGy. Gamma-irradiated resveratrol did not exert cytotoxicity to macrophages in dose ranges from 15 to 70kGy; therefore, 70kGy gamma-irradiated resveratrol was used as the maximum dose throughout subsequent experiments. Treatment of LPS-stimulated macrophages with 70kGy gamma-irradiated resveratrol resulted in a dose-dependent decrease in iNOS-mediated NO, PGE2, and pro-inflammatory cytokine level, such as TNF-α, IL-6 and IL-1ß. 70kGy gamma-irradiated resveratrol significantly inhibited cyclooxygenase-2 levels, as well as the expression of cell surface molecules, such as CD80 and CD86, in LPS-induced macrophages. Furthermore, the inhibitory action of these pro-inflammatory mediators occurred through an inhibition of MAPKs (ERK1/2, p38 and JNK) and NF-κB signaling pathways based on a toll-like receptor 4 in macrophages, which may be closely mediated with the radiolysis products of resveratrol transformed by gamma-irradiation. From these findings, it seems likely that gamma irradiation can be an effective tool for a reduction of the toxicity and play a potent role in the treatment of inflammatory disease.


Asunto(s)
Antiinflamatorios/farmacología , Antiinflamatorios/efectos de la radiación , Rayos gamma , Macrófagos/efectos de los fármacos , Estilbenos/farmacología , Estilbenos/efectos de la radiación , Animales , Antiinflamatorios/química , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Dinoprostona/metabolismo , Femenino , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Estructura Molecular , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Resveratrol , Transducción de Señal/efectos de los fármacos , Estilbenos/química , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
13.
Food Chem Toxicol ; 74: 255-64, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25447760

RESUMEN

Genistein was irradiated with γ-irradiation at doses of 0, 10, 30, 50, 100, and 150 kGy. We observed that the decrease in the genistein peak after gamma irradiation was concomitant with the appearance of several new peaks. 150 kGy gamma-irradiated genistein did not exert cytotoxicity in macrophages, and inhibited inducible nitric oxide synthase-mediated nitric oxide production and pro-inflammatory cytokines level, such as tumor necrosis factor-α, interleukin-6 and interleukin-1ß, in lipopolysaccharide (LPS)-induced macrophages. The treatment of LPS-stimulated macrophages with 150 kGy gamma-irradiated genistein resulted in a significant decrease in cyclooxygenase-2 levels, as well as the expression of cell surface molecules, such as CD80 and CD86. Furthermore, we also found that the anti-inflammatory action of 150 kGy gamma-irradiated genistein occurred through an inhibition of mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, p38 and c-Jun N-terminal kinase) and nuclear factor-κB signaling pathways based on a toll-like receptor 4 in macrophages, which may be speculated that several radiolysis products of genistein transformed by gamma-irradiation induce the inhibition of pro-inflammatory mediators. From these findings, it seems likely that gamma-irradiated genistein could play a potent role in the treatment of inflammatory disease as a value-added product in the medical industry.


Asunto(s)
Antiinflamatorios/farmacología , Antiinflamatorios/efectos de la radiación , Genisteína/farmacología , Genisteína/efectos de la radiación , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Animales , Antiinflamatorios/química , Antígeno B7-1/biosíntesis , Antígeno B7-2/biosíntesis , Línea Celular , Proliferación Celular/efectos de los fármacos , Alimentos Funcionales , Rayos gamma , Genisteína/química , Ratones , Óxido Nítrico/metabolismo , Receptor Toll-Like 4/efectos de los fármacos
14.
Appl Radiat Isot ; 90: 265-73, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24859334

RESUMEN

Human radiation exposure is increasing due to radiation development in science and technology. The development of radioprotective agents is important for protecting patients from the side effects of radiotherapy and for protecting the public from unwanted irradiation. Radioprotective agents are used to reduce the damage caused by radiation in healthy tissues. There are several classes of radioprotective compounds that are under investigation. Analgesics and anti-inflammatory compounds are being considered for treating or preventing the effects of damage due to radiation exposure, or for increasing the chance of survival after exposure to a high dose of radiation. In this study, we investigated the radioprotective effects of some analgesic and anti-inflammatory compounds by evaluating buildup factors. The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) were calculated to select compounds in a 0.015-15 MeV energy region up to a penetration depth of 40 mfp (mean free path). Variations of EABF and EBF with incident photon energy and penetration depth elements were also investigated. Significant variations in both EABF and EBF values were observed for several compounds at the moderate energy region. At energies below 0.15 MeV, EABF and EBF values increased with decreasing equivalent atomic number (Z(eq)) of the samples. In addition, EABF and EBF were the largest for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06 MeV, respectively, and the EABF value was 0.1 MeV for aceclofenac. From these results, we concluded that the buildup of photons is less for aceclofenac compared to other materials.


Asunto(s)
Absorción de Radiación , Antiinflamatorios/química , Antiinflamatorios/efectos de la radiación , Modelos Químicos , Fotones , Protectores contra Radiación/química , Protectores contra Radiación/efectos de la radiación , Simulación por Computador , Ensayo de Materiales
15.
Sci Rep ; 4: 4732, 2014 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-24751752

RESUMEN

We conducted a preliminary investigation of the effects of visible light irradiation on plant extracts, and we observed a strong suppressive effect on interleukin (IL) 2 expression with the inhibition of c-Jun amino-terminal kinase (JNK) phosphorylation in Jurkat cells by visible light irradiation to ethanol extract from green soybeans (LIEGS). This effect was produced only by extracts from green soybeans (Glycine max) and not other-color soybeans. LIEGS suppressed the lipopolysaccharide-induced IL-6, IL-12 and TNF-α expression levels in human monocyte THP-1 cells in a concentration-dependent manner. LIEGS was applied for 8 weeks to NC/Nga mice. LIEGS suppressed the development of atopic dermatitis (AD)-like skin lesions and reduced the dermatitis scores of the mice. The light irradiation changed the various types of small-molecule compounds in extracts. Visible light irradiation to daidzein with chlorophyll b induced a novel oxidative product of daidzein. This product suppressed IL-2 expression in Jurkat cells.


Asunto(s)
Antiinflamatorios/farmacología , Antiinflamatorios/efectos de la radiación , Glycine max/química , Luz , Extractos Vegetales/farmacología , Extractos Vegetales/efectos de la radiación , Animales , Antiinflamatorios/química , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Modelos Animales de Enfermedad , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-2/biosíntesis , Células Jurkat , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Extractos Vegetales/química
16.
Int J Pharm ; 452(1-2): 124-7, 2013 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-23639290

RESUMEN

A certain number of filters have notable anti-inflammatory properties with percentage inhibition of PMA-induced edema in mice at over 70%. The question arose as to whether this effect was likely to continue after UV irradiation. It can be noted that 7 filters retain an equivalent anti-inflammatory effect before and after 2h of irradiation in a Suntest device (650 W/m(2)). For 9 filters, the anti-inflammatory effect decreases and for 5 filters, the anti-inflammatory effect increases. Various behaviors should be noted. 3 groups of substances can be distinguished: such as phenylbenzimidazole sulfonic acid which loses its anti-inflammatory character after irradiation (the percentage inhibition falls from 80 to 44%), oxybenzone which retains a constant anti-inflammatory character (89% inhibition before and after irradiation and also octyl methoxycinnamate which becomes very anti-inflammatory (with a percentage inhibition of 93%). The same phenomenon is observed in the case of commercial products. This should be made known as it can have a considerable impact on the results which are displayed on the packaging of sun products.


Asunto(s)
Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos de la radiación , Edema/tratamiento farmacológico , Protectores Solares/administración & dosificación , Protectores Solares/efectos de la radiación , Rayos Ultravioleta , Animales , Oído/patología , Edema/inducido químicamente , Edema/patología , Emulsiones , Masculino , Ratones , Acetato de Tetradecanoilforbol , Óxido de Zinc/administración & dosificación , Óxido de Zinc/efectos de la radiación
17.
J Pharm Biomed Anal ; 47(4-5): 771-7, 2008 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-18423938

RESUMEN

Hydrocortisone 21-acetate (HCA) in methanol solution undergoes photodegradation under UVB light, as monitored by HPLC. Five main photoproducts have been isolated and characterized by means of NMR and mass spectroscopy. One of them derives from a Norrish I photoreaction which cleaves the C17-C20 bond of the steroid yielding the andro-derivative, a second product comes from a Yang-type photorearrangement which links C18 to C20 yielding a cyclobutane adduct. The former photoproduct, in turn, undergoes further photolysis giving rise to various photoproducts, of which three have been characterized. The first is a stereoisomer of the andro-derivative, the others arise from the opening of the five-membered ring. HCA also proved photounstable in the solid state and in a commercial formulation for topical use, thus confirming the requirements of the Pharmacopeias for light protection of this drug. Indeed, experiments on LPS-stimulated THP-1 cells demonstrated the loss of anti-inflammatory activity when HCA was UVB-photodegraded. The radical mechanism involved in HCA photolysis seems also responsible for the in vitro photohemolytic effect and lipid peroxidation induced by HCA in combination with UVB light.


Asunto(s)
Antiinflamatorios/efectos de la radiación , Hidrocortisona/análogos & derivados , Fotólisis , Rayos Ultravioleta , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Medios de Cultivo Condicionados/análisis , Medios de Cultivo Condicionados/química , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Eritrocitos/efectos de la radiación , Hemólisis/efectos de la radiación , Humanos , Hidrocortisona/química , Hidrocortisona/farmacología , Hidrocortisona/efectos de la radiación , Interleucina-1beta/análisis , Leucemia Monocítica Aguda/patología , Ácido Linoleico/efectos de la radiación , Peroxidación de Lípido/efectos de la radiación , Macrófagos/efectos de los fármacos , Espectrometría de Masas , Ratones , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Fotobiología , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo
18.
Gastroenterology ; 126(2): 520-8, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14762789

RESUMEN

BACKGROUND & AIMS: We tested whether the attenuation of experimental colitis by live probiotic bacteria is due to their immunostimulatory DNA, whether toll-like receptor (TLR) signaling is required, and whether nonviable probiotics are effective. METHODS: Methylated and unmethylated genomic DNA isolated from probiotics (VSL-3), DNAse-treated probiotics and Escherichia coli (DH5 alpha) genomic DNA were administered intragastrically (i.g.) or subcutaneously (s.c.) to mice prior to the induction of colitis. Viable or gamma-irradiated probiotics were administered i.g. to wild-type mice and mice deficient in different TLR or in the adaptor protein MyD88, 10 days prior to administration of dextran sodium sulfate (DSS) to their drinking water and for 7 days thereafter. RESULTS: Intragastric and s.c. administration of probiotic and E. coli DNA ameliorated the severity of DSS-induced colitis, whereas methylated probiotic DNA, calf thymus DNA, and DNase-treated probiotics had no effect. The colitis severity was attenuated to the same extent by i.g. delivery of nonviable gamma-irradiated or viable probiotics. Mice deficient in MyD88 did not respond to gamma-irradiated probiotics. The severity of DSS-induced colitis in TLR2 and TLR4 deficient mice was significantly decreased by i.g. administration of gamma-irradiated probiotics, whereas, in TLR9-deficient mice, gamma-irradiated probiotics had no effect. CONCLUSIONS: The protective effects of probiotics are mediated by their own DNA rather than by their metabolites or ability to colonize the colon. TLR9 signaling is essential in mediating the anti-inflammatory effect of probiotics, and live microorganisms are not required to attenuate experimental colitis because nonviable probiotics are equally effective.


Asunto(s)
Antiinflamatorios/farmacología , Colitis/patología , Colitis/fisiopatología , Proteínas de Unión al ADN/metabolismo , Probióticos/farmacología , Receptores de Superficie Celular/metabolismo , Transducción de Señal , Absorción , Adyuvantes Inmunológicos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/efectos de la radiación , Colitis/inducido químicamente , ADN/aislamiento & purificación , ADN/farmacología , ADN Bacteriano/farmacocinética , Sulfato de Dextran , Escherichia coli/genética , Rayos gamma , Ratones , Ratones Endogámicos , Probióticos/química , Probióticos/efectos de la radiación , Índice de Severidad de la Enfermedad , Receptor Toll-Like 9
19.
J Org Chem ; 68(11): 4361-6, 2003 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-12762737

RESUMEN

The photochemistry of six pregna-1,4-dien-3,20-diones has been compared and found to involve both the cyclohexadienone moiety in ring A and the isolated ketone at C-20. The two reactions take place proportionally to the fraction of light absorbed by each chromophore. The cross-conjugated ketone absorbs predominantly or exclusively at both 254 and 366 nm and undergoes the "lumi" rearrangement to bicyclo[3.1.0]hex-3-en-2-one. The quantum yield of the reaction diminished somewhat with increasing lambda(exc), e.g., for prednisolone Phi(254) (nm) = 0.42, Phi(366) (nm) = 0.3. A much stronger lowering is caused by halogen substitution in position 9 (by a factor of 3 for F, >50 for Cl), apparently due to a shortened triplet lifetime caused by heavy atom effect. At 310 nm, both chromophores absorb to a comparable degree and both may react. The reaction at C(20) ketone involves either quite efficient alpha-cleavage (C(17)-C(20)) for compounds bearing an acetal or hydroxyl function at C(17) or less effective (by a factor of ca. 10) hydrogen abstraction from the 18-methyl group in the other cases (finally resulting in Norrish II fragmentation or Yang cyclization). The results allow generalizing how the substitution pattern surrounding each chromophore affects the photoreactivity at that site and the competition between the two modes, allowing predicting the photochemistry of this family of antiinflammatory drugs.


Asunto(s)
Antiinflamatorios/química , Fotoquímica , Pregnadienos/química , Antiinflamatorios/efectos de la radiación , Catálisis , Química Orgánica/métodos , Estructura Molecular , Prednisolona/química , Pregnadienos/efectos de la radiación
20.
AAPS PharmSciTech ; 3(2): E8, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12916945

RESUMEN

The purpose of this study was to examine the viscoelastic properties of topical creams containing various concentrations of microcrystalline cellulose and sodium carboxymethyl cellulose (Avicel(R) CL-611) as a stabilizer. Avicel CL-611 was used at 4 different levels (1%, 2%, 4%, and 6% dispersion) to prepare topical creams, and hydrocortisone acetate was used as a model drug. The viscoelastic properties such as loss modulus (G"), storage modulus (G'), and loss tangent (tan delta) of these creams were measured using a TA Instruments AR 1000 Rheometer and compared to a commercially available formulation. Continuous flow test to determine the yield stress and thixotropic behavior, and dynamic mechanical tests for determining the linear viscosity time sweep data, were performed. Drug release from the various formulations was studied using an Enhancer TM Cell assembly. Formulations containing 1% and 2% Avicel CL-611 had relative viscosity, yield stress, and thixotropic values that were similar to those of the commercial formulation. The elastic modulus (G') of the 1% and 2% formulation was relatively high and did not cross the loss modulus (G"), indicating that the gels were strong. In the commercial formulation, G' increased after preshearing and broke down after 600 seconds. The strain sweep tests showed that for all formulations containing Avicel CL-611, the G' was above G" with a good distance between them. The gel strength and the predominance of G' can be ranked 6% > 4% > 2%. The strain profiles for the 1% and 2% formulations were similar to those of the commercial formulation. The delta values for the 1% and 2% formulations were similar, and the formulations containing 4% Avicel CL-611 had lower delta values, indicating greater elasticity. Drug release from the commercial preparation was fastest compared to the formulations prepared using Avicel CL-611, a correlation with the viscoelastic properties. It was found that viscoelastic data, especially the strain sweep profiles of products containing Avicel CL-611 1% and 2%, correlated with the commercial formulation. Rheological tests that measure the viscosity, yield stress, thixotropic behavior, other oscillatory parameters such as G' and G" are necessary tools in predicting performance of semisolids.


Asunto(s)
Carboximetilcelulosa de Sodio/química , Celulosa/química , Hidrocortisona/análogos & derivados , Hidrocortisona/química , Bases Oleosas/química , Administración Tópica , Antiinflamatorios/química , Antiinflamatorios/metabolismo , Antiinflamatorios/efectos de la radiación , Carboximetilcelulosa de Sodio/metabolismo , Carboximetilcelulosa de Sodio/efectos de la radiación , Celulosa/metabolismo , Celulosa/efectos de la radiación , Cromatografía Líquida de Alta Presión/métodos , Almacenaje de Medicamentos/métodos , Elasticidad/efectos de la radiación , Hidrocortisona/metabolismo , Hidrocortisona/efectos de la radiación , Bases Oleosas/metabolismo , Bases Oleosas/efectos de la radiación , Reología/métodos , Estrés Mecánico , Tecnología Farmacéutica/instrumentación , Tecnología Farmacéutica/métodos , Viscosidad/efectos de la radiación
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