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1.
PLoS Pathog ; 17(8): e1009780, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34407148

RESUMEN

Triatomine assassin bugs comprise hematophagous insect vectors of Trypanosoma cruzi, the causative agent of Chagas disease. Although the microbiome of these species has been investigated to some extent, only one virus infecting Triatoma infestans has been identified to date. Here, we describe for the first time seven (+) single-strand RNA viruses (RpV1-7) infecting Rhodnius prolixus, a primary vector of Chagas disease in Central and South America. We show that the RpVs belong to the Iflaviridae, Permutotetraviridae and Solemoviridae and are vertically transmitted from the mothers to the progeny via transovarial transmission. Consistent with this, all the RpVs, except RpV2 that is related to the entomopathogenic Slow bee paralysis virus, established persistent infections in our R. prolixus colony. Furthermore, we show that R. prolixus ovaries express 22-nucleotide viral siRNAs (vsiRNAs), but not viral piRNAs, that originate from the processing of dsRNA intermediates during viral replication of the RpVs. Interestingly, the permutotetraviruses and sobemoviruses display shared pools of vsiRNAs that might provide the basis for a cross-immunity system. The vsiRNAs are maternally deposited in the eggs, where they likely contribute to reduce the viral load and protect the developing embryos. Our results unveil for the first time a complex core virome in R. prolixus and begin to shed light on the RNAi-based antiviral defenses in triatomines.


Asunto(s)
Enfermedad de Chagas/transmisión , Insectos Vectores/virología , Virus ARN/fisiología , Rhodnius/virología , Triatoma/virología , Trypanosoma cruzi/fisiología , Viroma , Animales , Femenino , Genoma Viral , Oogénesis , Virus ARN/clasificación , ARN Interferente Pequeño/genética , Conejos , Transcriptoma
2.
Cytokine ; 152: 155826, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35158258

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the newly emerging lung disease pandemic COVID-19. This viral infection causes a series of respiratory disorders, and although this virus mainly infects respiratory cells, the small intestine can also be an important site of entry or interaction, as enterocytes highly express in angiotensin-2 converting enzyme (ACE) receptors. There are countless reports pointing to the importance of interferons (IFNs) with regard to the mediation of the immune system in viral infection by SARS-CoV-2. Thus, this review will focus on the main cells that make up the large intestine, their specific immunology, as well as the function of IFNs in the intestinal mucosa after the invasion of coronavirus-2.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/metabolismo , Mucosa Intestinal/metabolismo , Intestino Grueso/metabolismo , SARS-CoV-2/metabolismo , COVID-19/patología , Humanos , Mucosa Intestinal/lesiones , Mucosa Intestinal/patología , Mucosa Intestinal/virología , Intestino Grueso/lesiones , Intestino Grueso/patología , Intestino Grueso/virología
3.
Lasers Med Sci ; 37(1): 563-571, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33788097

RESUMEN

Photobiomodulation therapy (PBMT) is a non-thermal therapeutic procedure widely used in clinical practice. It is considered an effective modality of treatment for the control of various inflammatory conditions with fewer adverse effects as compared to conventional therapy. However, despite the clinical effects, the mechanisms of action and dosimetric parameters of PBMT are not fully understood. This study was performed to describe the effects of two different doses of PBMT on experimental models of inflammation. Male Swiss mice were administered with 0.9% of saline or phlogistic agents (carrageenan, dextran, serotonin, histamine, or bradykinin) by intra-plantar injection and were treated with PBMT at a dose of 1 or 5 J/cm2; right after, the variation of the paw volume was made, and histopathological analysis and myeloperoxidase assay of the carrageenan-induced edematous paw tissues were performed. The action of PBMT on carrageenan-induced vascular permeability was further evaluated. Our results showed that PBMT (1 J/cm2) led to an improvement in paw edema induced by the phlogistic agents and further reduced the histological scores. Inhibition of neutrophil migration was observed following the administration of 1 and 5 J/cm2 of PBMT. However, only 1 J/cm2 of PBMT showed beneficial effects on carrageenan-induced edema. Laser at a dose of 1 J/cm2 showed cellular and vascular effects since it was able to reverse all the inflammatory parameters, and laser at a dose of 5 J/cm2 probably has only cellular effects in the presence of acute inflammation.


Asunto(s)
Terapia por Luz de Baja Intensidad , Animales , Antiinflamatorios/uso terapéutico , Edema/inducido químicamente , Inflamación/radioterapia , Masculino , Ratones , Modelos Teóricos , Ratas , Ratas Wistar
4.
RNA ; 23(7): 1097-1109, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28420675

RESUMEN

Piwi-interacting RNAs (piRNAs) are central components of the piRNA pathway, which directs transposon silencing and guarantees genome integrity in the germ cells of several metazoans. In Drosophila, piRNAs are produced from discrete regions of the genome termed piRNA clusters, whose expression relies on the RDC complex comprised of the core proteins Rhino, Deadlock, and Cutoff. To date, the RDC complex has been exclusively implicated in the regulation of the piRNA loci. Here we further elucidate the function of Cutoff and the RDC complex by performing genome-wide ChIP-seq and RNA-seq assays in the Drosophila ovaries and analyzing these data together with other publicly available data sets. In agreement with previous studies, we confirm that Cutoff is involved in the transcriptional regulation of piRNA clusters and in the repression of transposable elements in germ cells. Surprisingly, however, we find that Cutoff is enriched at and affects the expression of other noncoding RNAs, including spliceosomal RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). At least in some instances, Cutoff appears to act at a transcriptional level in concert with Rhino and perhaps Deadlock. Finally, we show that mutations in Cutoff result in the deregulation of hundreds of protein-coding genes in germ cells. Our study uncovers a broader function for the RDC complex in the Drosophila germline development.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Ovario/crecimiento & desarrollo , ARN Interferente Pequeño/metabolismo , ARN no Traducido/metabolismo , Proteínas de Unión al ARN/metabolismo , Animales , Inmunoprecipitación de Cromatina , Elementos Transponibles de ADN , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Femenino , Regulación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Mutación , Ovario/química , Proteínas de Unión al ARN/genética , Análisis de Secuencia de ARN/métodos
5.
Lasers Med Sci ; 33(9): 1983-1990, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29951878

RESUMEN

The purpose of the study is to investigate the effects of two doses of photobiomodulation (PBM) on inflammatory parameters including cell migration and oxidative stress in carrageenan-induced peritonitis models. Twenty-eight mice were divided into four groups: saline; untreated carrageenan (Cg; inflammation induced); and PMB treatment groups L1 and L5 (inflammation induced with carrageenan followed by laser irradiation at 1 and 5 J/cm2, respectively). After 30 min of inducing inflammation, laser irradiation was administered every hour, for 4 h. Peritoneal fluid was collected for analyses. The total leukocyte number in the peritoneal fluid in L1 (4.33 ± 2.34) and L5 (4.95 ± 2.86) after PBM was lower than that in Cg (10.93 ± 5.15 cells/ml). The average differential count of neutrophils in the Cg was 9.46 ± 4.31 cells/ml, which was higher than that in L1 (3.7 ± 2.08) and L5 (4.94 ± 2.57). Myeloperoxidase activity was also lower in L1 (1.89 ± 0.43) and L5 (4.84 ± 2.62) than in Cg (22.92 ± 4.52 UMPO/ml). Malondialdehyde content was lower in L1 (137.5 ± 12.33) and L5 (169.6 ± 22.77) than in Cg (345.7 ± 65.67 nmol/ml). Glutathione peroxidase concentration was significantly higher in L1 (155.2 ± 12.43) and L5 (145.9 ± 9.585) than in Cg (79.75 ± 9.567 µ/ml). Nitrite concentration was lower in L1 (0.3317 µM ± 0.0669) and L5 (0.2429 µM ± 0.0232) than in Cg (0.8380 µM ± 0.01615). Laser irradiation at 1 and 5 J/cm2 reversed the inflammation (as indicated by neutrophil infiltration and oxidative stress).


Asunto(s)
Movimiento Celular/efectos de la radiación , Terapia por Luz de Baja Intensidad , Neutrófilos/patología , Estrés Oxidativo , Peritonitis/patología , Peritonitis/radioterapia , Animales , Carragenina , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Nitratos/metabolismo , Nitritos/metabolismo , Estrés Oxidativo/efectos de la radiación , Peroxidasa/metabolismo
6.
Head Neck ; 46(6): 1340-1350, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38445804

RESUMEN

INTRODUCTION: Cervical disease control might be challenging in advanced thyroid cancer (DTC). Indications for cervical external beam radiation therapy (EBRT) are controversial. PURPOSE: To identify clinical and molecular factors associated with control of cervical disease with EBRT. METHODS: Retrospective evaluation and molecular analysis of the primary tumor DTC patients who underwent cervical EBRT between 1995 and 2022 was performed. RESULTS: Eighty adults, median age of 61 years, were included. T4 disease was present in 43.7%, lymph node involvement in 42.5%, and distant metastasis in 47.5%. Those with cervical progression were older (62.5 vs. 57.3, p = 0.04) with more nodes affected (12.1 vs. 2.8, p = 0.04) and had EBRT performed later following surgery (76.6 vs. 64 months, p = 0.05). EBRT associated with multikinase inhibitors showed longer overall survival than EBRT alone (64.3 vs. 37.9, p = 0.018) and better local disease control. Performing EBRT before radioiodine (RAI) was associated with longer cervical progression-free survival (CPFS) than was RAI before (67.5 vs. 34.5, p < 0.01). EBRT ≥2 years after surgery was associated with worse CPFS (4.9 vs. 34, p = 0.04). The most common molecular alterations were ERBB2, BRAF, FAT1, RET and ROS1 and TERT mutation was predictive of worse disease control after EBRT (p = 0.04). CONCLUSION: Younger patients, with fewer affected nodes and treated earlier after surgery had better cervical disease control. Combination of EBRT with MKI improved OS. TERT mutation might indicate worse responders to EBRT; however, further studies are necessary to clarify the role of molecular testing in selecting candidates for cervical EBRT.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias de la Tiroides , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Masculino , Estudios Retrospectivos , Anciano , Adulto , Neoplasia Residual , Radioisótopos de Yodo/uso terapéutico , Tiroidectomía , Factores de Tiempo
7.
J Ethnopharmacol ; 324: 117707, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38232858

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The plants of the genus Casimirella ampla (Miers) (C. ampla) are extensively used in folk medicine. For a long time, rural communities have been using extracts from its roots for food and therapeutic purposes. The extract is rich in diterpenoid annonalide (Annona), which has antiophidic, anti-inflammatory and antinociceptive properties. Inflammation is the body's primary defense mechanism against cell damage and invasion by pathogens, which can trigger acute and chronic inflammatory processes. The first line of treatment for this condition consists of the use of non-steroidal anti-inflammatory drugs, but these have numerous associated collateral damages, based on scientific knowledge about diterpenoids from C. ampla, as well as their already reported antinociceptive and anti-inflammatory properties. AIMS OF THE STUDY: Evaluate the effect of Annona in classic models of inflammation and pain. MATERIALS AND METHODS: Animals were pretreated with Annona (0.1, 1.0 and 10 mg/kg), or Tween 80 (2%), or indomethacin (Indo) (10 mg/kg) orally in the paw edema tests induced by carrageenan (Cg), serotonin (5-HT), histamine, bradykinin, 48/80 and, prostaglandin E2 (PGE2), evaluating microscopic lesion scores, migration of leukocytes to the peritoneal cavity, concentration of myeloperoxide (MPO), malonyldialdehyde (MDA) and glutathione (GSH), abdominal contortion test by acetic acid and formalin test. RESULTS: Treatment with Annona compound at a dose of 0.1 mg/kg was more effective in reducing inflammatory, oxidant and nociceptive parameters, as it reduced paw edema induced by carrageenan, through different mediators and migration of inflammatory cells. Furthermore, it worked by reducing the concentration of MPO, MDA, preserving GSH levels and reducing nociception caused by formalin and acetic acid.


Asunto(s)
Analgésicos , Magnoliopsida , Animales , Carragenina , Analgésicos/efectos adversos , Extractos Vegetales/efectos adversos , Antiinflamatorios/efectos adversos , Inflamación/tratamiento farmacológico , Glutatión/metabolismo , Magnoliopsida/metabolismo , Acetatos , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismo
8.
J Periodontol ; 93(1): 156-165, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33856704

RESUMEN

BACKGROUND: Periodontitis is a chronic inflammatory and multifactorial disease that affects the periodontal structures and can cause alterations in the hepatic tissue. The aim of the present study was to evaluate whether a diet with food restriction can decrease oral and liver alterations associated with ligature-induced periodontitis. METHODS: Twenty-four female Wistar rats were used in this study, randomized into three groups (n = 8 for each group): control (regular food); periodontitis (regular food + periodontitis induced with ligatures); and food restriction (diet with food restriction and periodontitis induction). The following periodontium parameters were analyzed tooth mobility (TM), probing pocket depth (PPD), gingival bleeding index (GBI), and alveolar bone height (ABH). In the liver, the levels of oxidative stress markers-malondialdehyde (MDA), glutathione (GSH), total cholesterol, and levels of myeloperoxidase (MPO) activity were measured. Liver samples were analyzed for histopathological score. In the blood tissue, the levels of enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, total cholesterol, and the high-density lipoprotein (HDL) were also evaluated. RESULTS: The animals that received a diet with food restriction + periodontitis showed a decrease in hepatic histopathological score (P < 0.05) when compared with the periodontitis group, the same for glucose, total cholesterol, ALT, AST, and ABH data. The group with food restriction + periodontitis showed a decrease in the histopathological liver score (P < 0.05) compared with the group with periodontitis. CONCLUSION: This study revealed that food restriction reduced oral damages, as well as hepatic, blood and alveolar bone alterations associated with ligature-induced periodontitis in rats.


Asunto(s)
Pérdida de Hueso Alveolar , Periodontitis , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/prevención & control , Animales , Colesterol , Femenino , Glucosa , Glutatión , Hígado/patología , Periodontitis/complicaciones , Ratas , Ratas Wistar
9.
Sci Rep ; 11(1): 1918, 2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33479356

RESUMEN

Rhodnius prolixus is a Triatominae insect species and a primary vector of Chagas disease. The genome of R. prolixus has been recently sequenced and partially assembled, but few transcriptome analyses have been performed to date. In this study, we describe the stage-specific transcriptomes obtained from previtellogenic stages of oogenesis and from mature eggs. By analyzing ~ 228 million paired-end RNA-Seq reads, we significantly improved the current genome annotations for 9206 genes. We provide extended 5' and 3' UTRs, complete Open Reading Frames, and alternative transcript variants. Strikingly, using a combination of genome-guided and de novo transcriptome assembly we found more than two thousand novel genes, thus increasing the number of genes in R. prolixus from 15,738 to 17,864. We used the improved transcriptome to investigate stage-specific gene expression profiles during R. prolixus oogenesis. Our data reveal that 11,127 genes are expressed in the early previtellogenic stage of oogenesis and their transcripts are deposited in the developing egg including key factors regulating germline development, genome integrity, and the maternal-zygotic transition. In addition, GO term analyses show that transcripts encoding components of the steroid hormone receptor pathway, cytoskeleton, and intracellular signaling are abundant in the mature eggs, where they likely control early embryonic development upon fertilization. Our results significantly improve the R. prolixus genome and transcriptome and provide novel insight into oogenesis and early embryogenesis in this medically relevant insect.


Asunto(s)
Enfermedad de Chagas/genética , Ovario/metabolismo , Rhodnius/genética , Transcriptoma/genética , Animales , Enfermedad de Chagas/parasitología , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/genética , Genoma de los Insectos/genética , Humanos , Insectos Vectores/genética , Insectos Vectores/parasitología , Oogénesis/genética , Ovario/crecimiento & desarrollo , Rhodnius/parasitología , Trypanosoma cruzi/genética , Trypanosoma cruzi/patogenicidad
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.
J Pharm Pharmacol ; 73(4): 496-504, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33793830

RESUMEN

OBJECTIVE: To evaluate the participation of the phosphatidylinositol 3-kinase pathway in the liver damage caused by nimesulide. METHODS: Liver damage been induced by nimesulide. Mice were treated with either 2% dimethyl sulfoxide or AS605240, a phosphatidylinositol 3-kinase gamma pathway antagonist. Blood samples were collected for function assays of liver. The liver was removed for analysis of liver weight/animal weight ratio, histopathological parameters, oxidative and nitrous stress, cytokine levels, and the immunostaining for cyclooxygenase 2 and nuclear factor kappa B. KEY FINDINGS: Liver injured by nimesulide and treated with phosphatidylinositol 3-kinase gamma inhibitor significantly reversed (P < 0.05) the damage; it decreased the liver weight/animal weight ratio, histopathological scores, and neutrophil infiltration, consequently reducing oxidative stress. In addition, we show that phosphatidylinositol 3-kinase gamma is associated with hepatic damage induced by nimesulide, because it altered liver function and increased the protein immunostaining of cyclooxygenase 2 and nuclear factor kappa B in the liver tissue of nimesulide-treated animals. CONCLUSIONS: The findings from the present study allows us to infer that nimesulide causes liver damage through the phosphatidylinositol 3-kinase gamma pathway.


Asunto(s)
Fosfatidilinositol 3-Quinasa/metabolismo , Sulfonamidas , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Ciclooxigenasa/toxicidad , Dimetilsulfóxido/farmacología , Depuradores de Radicales Libres/farmacología , Ratones , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Quinoxalinas/farmacología , Sulfonamidas/farmacología , Sulfonamidas/toxicidad , Tiazolidinedionas/farmacología , Resultado del Tratamiento
12.
Int J Biol Macromol ; 159: 966-975, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32450322

RESUMEN

The present work aimed at carrying out the isolation and biochemical characterization of a sulfated polysaccharide fraction (PLS) from the marine algae Gracilaria intermedia and investigating its anti-inflammatory and antinociceptive potential. PLS was obtained through enzymatic digestion with papain and analyzed by means of gel permeation chromatography and Nuclear Magnetic Resonance to 1H and 13C. In order to evaluate the potential of anti-inflammatory action of PLS, we performed paw edema induced by carrageenan, dextran, compound 48/80, histamine and serotonin. In addition, we also measured the concentration of myeloperoxidase, cytokines, the count of inflammatory cells and performed tests of the nociception. The PLS isolated was of high purity and free of contaminants such as proteins, and had molecular weight of 410 kDa. The same macromolecule was able to decrease the paw edema induced by all inflammatory agents (P < 0.05), myeloperoxidase (MPO) activity, neutrophil migration and IL-1ß levels. It also decreased acetic acid-induced writhing (P < 0.05) and formalin-induced paw licking time (P < 0.05), but no in hot plate test. In summary, the PLS decreased the inflammatory response by reducing neutrophil migration and modulating IL-1ß production and antinociceptive effects by a peripheral mechanism dependent on the down-modulation of the inflammatory mediators.


Asunto(s)
Analgésicos/química , Analgésicos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Gracilaria/química , Polisacáridos/química , Polisacáridos/farmacología , Sulfatos/química , Animales , Biomarcadores , Movimiento Celular , Citocinas/metabolismo , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Estructura Molecular , Peroxidasa/metabolismo , Análisis Espectral , Relación Estructura-Actividad
13.
Eur J Pharmacol ; 873: 172974, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32027888

RESUMEN

Gabapentin is an anticonvulsant drug that is also used for post-herpetic neuralgia and neuropathic pain. Recently, gabapentin showed anti-inflammatory effect. Nuclear factor kappa B (NFκB) is a regulator of the inflammatory process, and Peroxisome Proliferator-activated Receptor gamma (PPAR-gamma) is an important receptor involved in NFκB regulation. The aim of the present work was to study the potential role of PPAR-gamma receptor in gabapentin-mediated anti-inflammatory effects in a colitis experimental model. We induced colitis in rats using trinitrobenzenosulfonic acid and treated them with gabapentin and bisphenol A dicyldidyl ether (PPAR-gamma inhibitor). Macroscopic lesion scores, wet weight, histopathological analysis, mast cell count, myeloperoxidase, malondialdehyde acid, glutathione, nitrate/nitrite, and interleukin levels in the intestinal mucosa were determined. In addition, western blots were performed to determine the expression of Cyclooxygenase-2 (COX-2) and NFκB; Nitric Oxide Inducible Synthase (iNOS) and Interleukin 1 beta (IL-1ß) levels were also determined. Gabapentin was able to decrease all inflammatory parameters macroscopic and microscopic in addition to reducing markers of oxidative stress and cytokines such as IL-1ß and Tumor Necrosis Factor alpha (TNF-α) as well as enzymes inducible nitric oxide synthase and cyclooxygenase 2 and inflammatory genic regulator (NFκB). These effect attributed to gabapentin was observed to be lost in the presence of the specific inhibitor of PPAR-gamma. Gabapentin inhibits bowel inflammation by regulating mast cell signaling. Furthermore, it activates the PPAR-gamma receptor, which in turn inhibits the activation of NFκB, and consequently results in reduced activation of inflammatory genes involved in inflammatory bowel diseases.


Asunto(s)
Colitis/tratamiento farmacológico , Gabapentina/uso terapéutico , PPAR gamma/efectos de los fármacos , Animales , Compuestos de Bencidrilo/uso terapéutico , Colitis/inducido químicamente , Colitis/patología , Citocinas/metabolismo , Glutatión/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Masculino , Malondialdehído/metabolismo , Mastocitos/efectos de los fármacos , FN-kappa B/metabolismo , PPAR gamma/antagonistas & inhibidores , Peroxidasa/metabolismo , Fenoles/uso terapéutico , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Ácido Trinitrobencenosulfónico
14.
J Ethnopharmacol ; 248: 112303, 2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-31614204

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: There are many reports of pharmacological activities of extracts and fractions of different vegetable-derived products in the scientific literature and in folk medicine. Ethnopharmacological use of these products by various communities continues to be extensively explored, and they account for more than half of all medications used worldwide. Polysaccharides (PLS) extracted from plants such as Morinda Citrifolia Linn present therapeutic potential in treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). AIM OF THE STUDY: To evaluate the anti-inflammatory action of Noni-PLS against the intestinal damage in UC induced by acetic acid in mice. MATERIALS AND METHODS: In acetic acid-induced colitis, the mice were treated intraperitoneally (ip) with Noni-PLS (0.1, 0.3, and 3.0 mg/kg) or subcutaneously (sc) with dexamethasone (2.0 mg/kg) 30 min before euthanasia to determine the best dose of Noni-PLS with an anti-inflammatory effect in the course of UC. The colonic tissue samples were collected for macroscopic, wet weight, microscopic and biochemical (myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), nitrate/nitrite (NO3/NO2), cytokines, cyclooxygenase (COX-2) and inducible nitric oxide (iNOS)) analyses. RESULTS: Treatment with Noni-PLS reduced the intestinal damage induced by acetic acid as it reduced macroscopic and microscopic scores and the wet weight of the colon. In addition, MPO activity and levels of GSH, MDA, NO3/NO2, pro-inflammatory cytokines, and COX-2 expression reduced. CONCLUSIONS: This study suggests that Noni-PLS exhibits anti-inflammatory action against intestinal damage by reducing inflammatory cell infiltration, oxidative stress, pro-inflammatory action of cytokines, COX-2 and iNOS expression in the inflamed colon. Noni-PLS shows therapeutic potential against inflammatory disorders like UC.


Asunto(s)
Antiinflamatorios/uso terapéutico , Colitis/tratamiento farmacológico , Morinda , Polisacáridos/uso terapéutico , Ácido Acético , Animales , Antiinflamatorios/farmacología , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Ciclooxigenasa 2/metabolismo , Frutas , Glutatión/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Nitratos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Nitritos/metabolismo , Peroxidasa/metabolismo , Polisacáridos/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
15.
Int J Biol Macromol ; 132: 1-8, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-30926484

RESUMEN

Sulfated polysaccharides (PLS) extracted from the marine algae of the genus Gracilaria showed biological activity in different inflammatory models, except for periodontitis. Thus, this study aimed to evaluate the effectiveness of the treatment with PLS from Gracilaria caudata in ligature-induced periodontitis. 40 animals distributed into 5 groups were used (the control group (unligated), the ligated untreated group, and the ligated groups treated with 2.5, 5.0 and 10.0 mg/kg of PLS with intraperitoneal injection, respectively). After 20 days of treatment, the animals were killed and the following parameters were evaluated: Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD), Myeloperoxidase (MPO) activity, Alveolar Bone Loss (ABL) for periodontal tissues; histopathological examination of gingival and liver tissues (Steatosis score); glutathione and malondialdehyde concentrations in the liver, serum levels of alanine aminotransferase and aspartate aminotransferase. The data revealed that treatment with 2.5 mg/kg of PLS showed the best anti-inflammatory effects with reduction of GBI, PPD and MPO activity, as well as oxidative stress and steatosis in liver. Our results indicated that the adjunct treatment with PLS from Gracilaria caudata could prevent the periodontal and hepatic tissue alteration caused by periodontitis.


Asunto(s)
Gracilaria/química , Periodontitis/patología , Polisacáridos/química , Polisacáridos/farmacología , Sulfatos/química , Animales , Biomarcadores/metabolismo , Citoprotección/efectos de los fármacos , Femenino , Ligadura/efectos adversos , Hígado/efectos de los fármacos , Hígado/patología , Malondialdehído/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Periodontitis/etiología , Periodontitis/metabolismo , Ratas , Ratas Wistar
16.
Life Sci ; 231: 116535, 2019 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-31175857

RESUMEN

Latex proteins from P. pudica (LPPp) have anti-inflammatory activity. In the present study, LPPp was evaluated to protect animals against inflammatory ulcerative colitis (UC). UC was induced by intracolonic instillation of a 6% acetic acid solution and the animals received LPPp (10, 20 or 40 mg/kg) by intraperitoneal route 1 h before and 17 h after acetic acid injection. Eighteen hours after instillation of acetic acid, the mice were euthanized and the colons were excised to determine the wet weight, macroscopic and microscopic lesion scores, myeloperoxidase (MPO) activity, IL1-ß levels, glutathione (GSH) and malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity. The results revealed that LPPp treatment (40 mg/kg) had a protective effect on acetic acid-induced colitis by reducing the wet weight, macroscopic and microscopic scores of intestinal lesions and colonic MPO activity. Additionally, LPPp inhibited tissue oxidative stress, since decreases in GSH consumption, MDA concentration and SOD activity were observed. The treatment with LPPp reduced the levels of cytokine IL-1ß, contributing to the reduction of colon inflammation. Biochemical investigation showed that LPPp comprises a mixture of proteins containing proteinases, chitinases and proteinase inhibitors. These data suggest that LPPp has a protective effect against intestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration, cytokine release and oxidative stress.


Asunto(s)
Apocynaceae/química , Colitis/tratamiento farmacológico , Látex/farmacología , Proteínas de Plantas/farmacología , Ácido Acético , Animales , Apocynaceae/metabolismo , Colitis/inducido químicamente , Colitis/metabolismo , Colon/efectos de los fármacos , Citocinas/metabolismo , Glutatión/metabolismo , Inflamación/tratamiento farmacológico , Interleucina-1beta/metabolismo , Intestinos/patología , Látex/aislamiento & purificación , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Proteínas de Plantas/aislamiento & purificación , Sustancias Protectoras/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
17.
PLoS Negl Trop Dis ; 12(10): e0006760, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30303955

RESUMEN

The piRNA pathway is a surveillance system that guarantees oogenesis and adult fertility in a range of animal species. The pathway is centered on PIWI clade Argonaute proteins and the associated small non-coding RNAs termed piRNAs. In this study, we set to investigate the evolutionary conservation of the piRNA pathway in the hemimetabolous insect Rhodnius prolixus. Our transcriptome profiling reveals that core components of the pathway are expressed during previtellogenic stages of oogenesis. Rhodnius' genome harbors four putative piwi orthologs. We show that Rp-piwi2, Rp-piwi3 and Rp-ago3, but not Rp-piwi1 transcripts are produced in the germline tissues and maternally deposited in the mature eggs. Consistent with a role in Rhodnius oogenesis, parental RNAi against the Rp-piwi2, Rp-piwi3 and Rp-ago3 results in severe egg laying and female adult fertility defects. Furthermore, we show that the reduction of the Rp-piwi2 levels by parental RNAi disrupts oogenesis by causing a dramatic loss of trophocytes, egg chamber degeneration and oogenesis arrest. Intriguingly, the putative Rp-Piwi2 protein features a polyglutamine tract at its N-terminal region, which is conserved in PIWI proteins encoded in the genome of other Triatomine species. Together with R. prolixus, these hematophagous insects are primary vectors of the Chagas disease. Thus, our data shed more light on the evolution of the piRNA pathway and provide a framework for the development of new control strategies for Chagas disease insect vectors.


Asunto(s)
Regulación de la Expresión Génica , Insectos Vectores/genética , Insectos Vectores/fisiología , Oogénesis , ARN Interferente Pequeño/metabolismo , Rhodnius/genética , Rhodnius/fisiología , Animales , Femenino , Perfilación de la Expresión Génica
18.
Int J Biol Macromol ; 112: 1122-1130, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29452186

RESUMEN

Seaweeds are sources of biomolecules with biological activities and pharmacological potential - for example, lectins, a group of proteins that can bind reversibly to carbohydrates or compounds containing them. The aim of this study was to elucidate the structural properties of a lectin extracted from the red seaweed Bryothamnion triquetrum (BtL) and to investigate its anti-inflammatory activity in mice. The lectin was purified by precipitation with ammonium sulfate and ion-exchange chromatography. Its secondary structure and tryptophan (Trp) microenvironment were analyzed by circular dichroism spectroscopy and steady-state fluorescence spectroscopy, respectively. The anti-inflammatory effect was evaluated by means of paw edema induced by carrageenan or dextran, myeloperoxidase activity in paw tissue, and by measurement of leukocyte and neutrophil migration and cytokine quantification in a peritonitis model. The secondary structure of BtL is mostly composed of ß-strands and unordered conformation, and it is quite resistant to extremes of pH and temperature, preserving the exposure of Trp residues under these conditions. In an assessment of biological activities, groups of mice were subjected to pretreatment with BtL before the inflammatory stimulus. BtL had anti-inflammatory effects in the models tested, and hence may be considered a molecule with potential to be used in the pharmaceutical industry.


Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Lectinas/química , Lectinas/farmacología , Rhodophyta/química , Algas Marinas/química , Animales , Antiinflamatorios/uso terapéutico , Carragenina , Movimiento Celular/efectos de los fármacos , Dextranos , Edema/tratamiento farmacológico , Edema/patología , Femenino , Hemaglutinación/efectos de los fármacos , Concentración de Iones de Hidrógeno , Interleucina-1beta/biosíntesis , Lectinas/aislamiento & purificación , Lectinas/uso terapéutico , Ratones , Peritonitis/tratamiento farmacológico , Peritonitis/patología , Peroxidasa/antagonistas & inhibidores , Peroxidasa/metabolismo , Estructura Secundaria de Proteína , Conejos , Espectrometría de Fluorescencia , Temperatura , Factor de Necrosis Tumoral alfa/biosíntesis
19.
Carbohydr Polym ; 197: 515-523, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-30007642

RESUMEN

Polysaccharides extracted from plants are very promising molecules in the field of pharmacotherapy. Knowing this, the aim of this study was to extract, characterize and evaluate the action of the polysaccharide of Morinda citrifolia Linn (Noni-PLS) in biological models of inflammatory processes. The characterization tests shown that sample refers to a heteropolysaccharide composed mainly of homogalacturonan and rhamnogalacturonan. This polysaccharide at dose of 10 mg/kg, when tested in our models of inflammation, showed significant activity in reducing carrageenan-induced paw oedema as well as all mediators edemas. This polysaccharide was able to inhibit the migration of leukocytes to the site of inflammation, and still reduced inflammatory nociception tests. This results, allows us to conclude that the polysaccharide extracted from Morinda citrifolia linn has anti-inflammatory potential since it reversed inflammatory parameters such as edema, leukocyte migration and nociception.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Edema/tratamiento farmacológico , Morinda/química , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Carragenina , Edema/inducido químicamente , Edema/patología , Masculino , Ratones , Tamaño de la Partícula , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Polisacáridos/química , Polisacáridos/aislamiento & purificación
20.
Biomed Pharmacother ; 102: 278-285, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29567541

RESUMEN

Epiisopiloturine (EPI) is an important imidazole alkaloid because of its pharmacological properties. The aim of this study was to investigate the effects of epiisopiloturine on inflammatory parameters of the colonic mucosa in a rat model of Crohn's disease (CD). For this, we induced colitis using trinitrobenzenosulfonic acid and determined myeloperoxidase (MPO), interleukin 1 ß (IL-1ß), glutathione (GSH), and malondialdehyde (MDA) levels in the intestinal mucosa. The location and expression of the inflammatory markers in the colon were investigated by immunohistochemistry for NO synthase induced (iNOS), interleukin 1 beta (IL-1ß), and cyclooxygenase-2 (COX-2) and western blotting (iNOS and COX-2), respectively. Compared with TNBS alone, epiisopiloturine at 1 mg/kg reduced the macroscopic and microscopic scores, wet weight of the colon, and neutrophilic infiltration and expression of the pro-inflammatory cytokine IL-1ß. Epiisopiloturine at 1 mg/kg maintained or restored GSH levels and simultaneously decreased MDA levels. Animals treated with epiisopiloturine exhibited reduced immunostaining for IL-1ß, iNOS, and COX-2 and reduced cell count per field. Epiisopiloturine reduced the expression of COX-2 and iNOS in the colon. Based on these findings, we conclude that epiisopiloturine at 1 mg/kg may be an important pharmacological tool against intestinal inflammatory diseases due to its inhibitory action on key enzymes and products involved in inflammation.


Asunto(s)
4-Butirolactona/análogos & derivados , Alcaloides/uso terapéutico , Antiinflamatorios/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Imidazoles/uso terapéutico , Peroxidación de Lípido/efectos de los fármacos , 4-Butirolactona/farmacología , 4-Butirolactona/uso terapéutico , Alcaloides/farmacología , Animales , Antiinflamatorios/farmacología , Enfermedad de Crohn/inmunología , Modelos Animales de Enfermedad , Femenino , Imidazoles/farmacología , Inflamación , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Ratas Wistar , Ácido Trinitrobencenosulfónico
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