RESUMEN
Acute and chronic colitis affect a huge proportion of the population world-wide. The etiology of colitis cases can be manifold, and diet can significantly affect onset and outcome of colitis. While many forms of acute colitis are easily treatable, chronic forms of colitis such as ulcerative colitis and Crohn's disease (summarized as inflammatory bowel diseases) are multifactorial with poorly understood pathogenesis. Inflammatory bowel diseases are characterized by exacerbated immune responses causing epithelial dysfunction and bacterial translocation. There is no cure and therapies aim at reducing inflammation and restoring intestinal barrier function. Unfortunately, most drugs can have severe side effects. Changes in diet and inclusion of nutritional supplements have been extensively studied in cell culture and animal models, and some supplements have shown promising results in clinical studies. Most of these nutritional supplements including vitamins, fatty acids and phytochemicals reduce oxidative stress and inflammation and have shown beneficial effects during experimental colitis in rodents induced by dextran sulphate sodium or 2,4,6-trinitrobenzene sulfonic acid, which remain the gold standard in pre-clinical colitis research. Here, we summarize the mechanisms through which such nutritional supplements contribute to epithelial barrier stabilization.
Asunto(s)
Colitis Ulcerosa/dietoterapia , Enfermedad de Crohn/dietoterapia , Suplementos Dietéticos , Mucosa Intestinal/efectos de los fármacos , Animales , Células CACO-2 , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Enfermedad de Crohn/inducido químicamente , Enfermedad de Crohn/patología , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Ácidos Grasos/administración & dosificación , Humanos , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/citología , Mucosa Intestinal/patología , Estrés Oxidativo/efectos de los fármacos , Permeabilidad/efectos de los fármacos , Fitoquímicos/administración & dosificación , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Resultado del Tratamiento , Ácido Trinitrobencenosulfónico/toxicidad , Vitaminas/administración & dosificaciónRESUMEN
Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic relapsing disorders of the intestines. They cause severe problems, such as abdominal cramping, bloody diarrhea, and weight loss, in affected individuals. Unfortunately, there is no cure yet, and treatments only aim to alleviate symptoms. Current treatments include anti-inflammatory and immunosuppressive drugs that may cause severe side effects. This warrants the search for alternative treatment options, such as nutritional supplements, that do not cause side effects. Before their application in clinical studies, such compounds must be rigorously tested for effectiveness and security in animal models. A reliable experimental model is the dextran sulfate sodium (DSS) colitis model in mice, which reproduces many of the clinical signs of ulcerative colitis in humans. We recently applied this model to test the beneficial effects of a nutritional supplement containing vitamins C and E, L-arginine, and ω3-polyunsaturated fatty acids (PUFA). We analyzed various disease parameters and found that this supplement was able to ameliorate edema formation, tissue damage, leukocyte infiltration, oxidative stress, and the production of pro-inflammatory cytokines, leading to an overall improvement in the disease activity index. In this article, we explain in detail the correct application of nutritional supplements using the DSS colitis model in C57Bl/6 mice, as well as how disease parameters such as histology, oxidative stress, and inflammation are assessed. Analyzing the beneficial effects of different diet supplements may then eventually open new avenues for the development of alternative treatment strategies that alleviate IBD symptoms and/or that prolong the phases of remission without causing severe side effects.
Asunto(s)
Colitis/patología , Suplementos Dietéticos , Animales , Arginina/farmacología , Ácido Ascórbico/farmacología , Colitis/inducido químicamente , Citocinas/genética , Citocinas/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Ácidos Grasos Omega-3/farmacología , Intestinos/patología , Leucocitos/citología , Leucocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Uniones Estrechas/metabolismoRESUMEN
The correct regulation of tissue barriers is of utmost importance for health. Barrier dysfunction accompanies inflammatory disorders and, if not controlled properly, can contribute to the development of chronic diseases. Tissue barriers are formed by monolayers of epithelial cells that separate organs from their environment, and endothelial cells that cover the vasculature, thus separating the blood stream from underlying tissues. Cells within the monolayers are connected by intercellular junctions that are linked by adaptor molecules to the cytoskeleton, and the regulation of these interactions is critical for the maintenance of tissue barriers. Many endogenous and exogenous molecules are known to regulate barrier functions in both ways. Proinflammatory cytokines weaken the barrier, whereas anti-inflammatory mediators stabilize barriers. Adrenomedullin (ADM) and intermedin (IMD) are endogenous peptide hormones of the same family that are produced and secreted by many cell types during physiologic and pathologic conditions. They activate certain G-protein-coupled receptor complexes to regulate many cellular processes such as cytokine production, actin dynamics and junction stability. In this review, we summarize current knowledge about the barrier-stabilizing effects of ADM and IMD in health and disease.