Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis.
Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Troxerutin (TRX), a semi-synthetic flavonoid extracted from Dimorphandra gardneriana, has been reported as a potent antioxidant and anti-inflammatory agent. In the present study, we aimed to evaluate the effect of TRX on 5-FU-induced intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, TRX-50, TRX-100, TRX-150, Celecoxib (CLX), and CLX + TRX-100. The weight of mice was measured daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis), levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), mast and goblet cell counts, immunohistochemical analysis, and cyclooxygenase-2 (COX-2) activity. Compared to the saline treatment, the 5-FU treatment induced intense weight loss and reduction in villus height. TRX treatment (100 mg/kg) prevented the 5-FU-induced histopathological changes and decreased oxidative stress by decreasing the MDA levels and increasing GSH concentration. TRX attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. TRX also reversed the depletion of goblet cells. Our findings suggest that TRX at a concentration of 100 mg/kg had chemopreventive effects on 5-FU-induced intestinal mucositis via COX-2 pathway.
Este artigo tem como objetivo investigar o uso da tecnologia 3D no ensino de anatomia. Os principais requisitos desse estudo consistem em saber se o uso da tecnologia 3D facilita o aprendizado dos conteúdos abordados no ensino de anatomia humana. Trata-se de um estudo preliminar que pode servir de parâmetros para uma formação crítica, reflexiva e criativa dos alunos da área da saúde com a utilização dos recursos tecnológicos 3D. Nesta revisão, realizada no período de setembro a outubro de 2019, buscou-se artigos indexados nas bases de dados eletrônicas PubMed, ScienceDirect e Google Scholar, publicados em português e inglês, de 2015 a 2019. Os descritores utilizados foram: “3D”, “ensino”, “anatomia humana”, “aprendizado”. Estudos de revisão, artigos com duplicidade de dados; títulos e / ou resumos que não atendem aos critérios de inclusão foram excluídos, bem como trabalhos com ausência de informações pertinentes, totalizando 14 artigos para análise nesta revisão. Embora a prospecção seja o método mais comum de ensino de anatomia, tecnologias recentes, como o software 3D, também são consideradas ferramentas de ensino úteis. Os alunos de graduação apresentaram como única desvantagem a necessidade de ter o recurso tecnológico pra criar ou replicar modelos 3D. A grande maioria dos trabalhos demonstraram satisfação dos estudantes quando estes utilizaram os modelos 3D. O presente trabalho demonstra que os modelos 3D são ferramentas viáveis e suplementares para o estudo da anatomia humana, porém ainda há necessidade de mais estudos para melhor forma de utilização dessas ferramentas no processo de ensino-aprendizagem da anatomia humana.
This work aimed the development and evaluation of the wound healing activity of films based on sodium alginate, polyvinyl alcohol (PVA) and Ca2+ loaded with Agaricus blazei Murill hydroalcoholic extract (AbE). Firstly, AbE was prepared using a previously standardized methodology. The films were prepared by casting technique and cross‐linked with Ca2+ using CaCl2 as cross‐linking agent. The physicochemical, morphological and water vapor barrier properties of the films were analyzed and the pre‐clinical efficacy was investigated against the cutaneous wound model in mice. The films showed barrier properties to water vapor promising for wound healing. AbE showed physical and chemical interactions between both polymers, noticed by Fourier transform infrared spectroscopy, X‐ray diffraction, scanning electron microscopy, and thermal analysis. The delivery of AbE in alginate/PVA films enhanced the antioxidant and wound healing properties of these polymers. Consequently, a reduction of malondialdehyde levels was observed, as well as an increase of the epidermis/dermis thickness and enhancement in collagen I deposition. Thus, these formulations are promising biomaterials for wound care and tissue repairing.
Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. This infection can particularly affect older adults, the most susceptible to CDI. Currently, the standard therapeutic measure is antibiotic therapy, which in turn increases the risk of recurrence of the infection by its collateral damage to the patient’s microbiota. Probiotics are live microorganisms capable of maintaining balance in the intestinal microbiota. This study aims to perform an integrative review of the protective benefit of probiotics in CDI and diarrhea associated with C. difficile. The PubMed, Scopus, and Web of Science databases, the 10-year time cutoff, and the Prism Flow diagram were used for data collection. We observed no consensus among the studies; however, three of the seven evaluated studies demonstrated that the use of probiotics in older adults could contribute to reducing the incidence of hospital-onset CDI. We also found that the studies evaluated a wide variety of microorganisms, particularly Saccharomyces boulardii, associated with beneficial effects. More research is needed to understand the successful use of probiotics in the prevention of CDI in hospitalized older adults receiving antibiotics.
Intestinal mucositis (MI), characterized by inflammation and ulceration of the intestinal mucosa, is one of the main causes of morbidity and mortality in chemotherapy patients (LEE et al., 2014).GOALSTo evaluate the action of the white angico polysaccharide on the histological changes in villi and crypts induced by 5‐FU in the intestinal mucosa;To verify the role of the white angico polysaccharide in the involvement of the cyclooxygenase‐2 (COX‐2) pathway in the 5‐FU induced intestinal mucositis model;METHODSThe experimental protocol was forwarded and approved by the Ethics Committee for Animal Use (CEUA) of UFC (3463140518). Intestinal mucositis was induced in mice with administration of 5‐FU, according to the methodology described by Carneiro‐Filho et al. (2004), in which the mice received on the first day of the experiment a single dose of 5‐FU (450 mg/kg) via intraperitoneal (i.p). The treatment was done using three doses of the white angico polysaccharide (100, 200, 400 mg/kg) one day after the injection of 5‐FU, the doses being based on Santos et al. (2013). The animals were divided into groups: Group I (Saline): saline solution 0.9% (0.1 mL/10g) and intraperitoneal (i.p), in parallel to the other groups treated throughout the study. Group II (5‐FU): on the first day of the experimental protocol will receive a single dose of 5‐FU (450 mg/kg) i.p. and will be treated with 0.9% saline solution (0.1 mL/10g) on the next four days. Group III (Angico best dose): 5‐FU (450 mg/kg) i.p on the first day of the experiment and was treated with angico diluted in distilled water. Group IV (Celecoxib): single dose of 5‐FU (450mg/kg) intraperitoneally (i.p) on the first day. On the following days of the experimental protocol only Celecoxib (7.5 mg/kg, i.p) was administered Group V (Celocoxib + Angico best dose): single dose of 5‐FU (450mg/kg) intraperitoneally (i.p) on the first day. On the second day of protocol, they was received white angico polysaccharide diluted in distilled water, and Celecoxib (7.5 mg/kg, i.p). After the histological processing, the morphometric evaluation was carried out with the aid of the ImageJ software, where the height of the villi and the depth of the crypts were measured. Immunohistochemistry for COX‐2 was then performed using the streptavidin‐biotin‐peroxidase method (HSU; RAINE, 1981)RRESULTSThe white Angico polysaccharide was able to statistically (p <0.05) prevent the shortening of villi and decrease the depth of the crypts caused by 5‐FU (Figure 1). The groups treated with angio 400 mg/kg, CLX and the CLX + angio combination (Figure 2) showed a statistically significant (p <0.05) reduction of the immunolabelled area for COX‐2 when compared to the 5‐FU group.CONCLUSIONThe white angico polysaccharide protected the intestinal mucosa and promoted a decrease in COX‐2 expression in the 5‐FU induced intestinal mucositis model.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Intestinal mucositis was induced by the administration of 5‐FU in a single dose of 450mg/kg on the first day of the protocol in Swiss mice, and groups of animals that received dosages of angico branco were treated between the second and the fifth day, culminating in euthanasia and removal of intestinal segments for further analysis. Initially, through histopathological and morphometric findings, the severity of mucositis was demonstrated in this study, through aspects related to tissue architecture, focusing on the reduction and vacuolization of intestinal villi, crypt necrosis, infiltration of inflammatory cells, loss of inflammation cell architecture, decreased villus/crypt ratio, caused in the group of animals that received the 5‐FU dose. However, the group of animals that were treated with angico branco gum at a dose of 400mg/kg, after induction of intestinal mucositis, attenuation of these deleterious effects promoted by 5‐FU was observed, among which we can mention: less inflammatory infiltrate, maintenance of cellular architecture, attenuation of villus shortening and crypt depth, decrease of crypt necrosis, also evidenced by the better villus/crypt ratio. These effects, however, were not seen in the ileum. Treatment with white angelic gum at doses of 100 mg/kg; 200 mg/kg and 400 mg/kg promoted a statistically significant reduction (p <0.05) in the number of mast cells when confronted with the 5‐FU group in the duodenum and jejunum. In contrast, treatment with white angico gum reversed the mastocytosis observed by the increase in mast cell count in the intestinal segments of animals submitted to mucositis. In addition, the saline group did not show an increase in mast cells when compared to the group with 5‐FU. Studies that evaluated the role of mast cells in mucositis also revealed the participation of these substances in the course of intestinal mucositis (PEREIRA JUNIOR, 2017; MIRANDA, 2018). The study by Nogueira et al. (2017) also demonstrated a significant increase in the number of total and degranulated mast cells in the intestinal segments of animals subjected to irinotecan‐induced intestinal mucositis, with a release of pro‐inflammatory mediators in the inflammatory condition. Through the results found in this study it can be concluded that the gum of angico reduced the mast cell count and preserved the number of goblet cells after induction of intestinal mucositis induced by 5‐FU in mice. White angico gum reduces the mast cell count in the duodenum, jejunum of mice subjected to intestinal mucositis induced by 5‐FU.
Introduction: In this study, we aimed to perform a literature review to investigate the existence of therapeutic proposals in 5-Fluoruracil-induced intestinal mucositis, which is a common side effect of chemotherapy treatment. The literature review was performed using PubMed, Science Direct, and Bireme between 2015 and 2019. The descriptors used " intestinal mucositis" AND " intestinal mucositis and 5-Fluorouracil". We excluded from the review studies, double data studies, titles and/or summaries that did not address therapeutic proposals, and articles not available in full. Were selected thirty-two articles, which had the objective of evaluating the effect of substances on the model of intestinal mucositis induced by 5-Fluorouracil; it is emphasized that no articles with clinical evaluation were found. On the other hand, several animal studies are being carried out with the main objective being the evaluation of probiotics, products of natural origin, and drug repurposing for the treatment of intestinal mucositis. The main morphological parameters evaluated were histological changes, inflammatory parameters, oxidative stress, intestinal permeability, microbiota homeostasis, cell apoptosis, and the number of goblet cells that are altered during the pathophysiology of intestinal mucositis. It was verified that there is still no evidence in the literature for the existence of effective clinical treatment for intestinal mucositis induced by 5-Fluorouracil. However, promising preclinical results were found with extracts of traditional plants, substances isolated from plants, and probiotics with emphasis on those of the genus Lactobacillus.
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