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1.
Nutrients ; 16(16)2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39203871

RESUMEN

Polyphenols are plant metabolites with potential anti-inflammatory and anti-proliferative effects, which may be advantageous for disorders like colorectal cancer (CRC). Despite promising in vitro and in vivo evidence, human clinical trials have yielded mixed results. The present study aimed to evaluate the clinical evidence of polyphenols for CRC prevention or treatment. A systematic review was performed according to PRISMA. Based on a PROSPERO registered protocol (CRD42024560044), online databases (PubMed and COCHRANE) were utilized for the literature search. A total of 100 studies articles were initially identified. After reviewing, 12 studies with a low risk of bias were selected, examining the effect of a variety of compounds. Curcumin demonstrated promise in various trials, mainly decreasing inflammatory cytokines, though results varied, and it did not lower intestinal adenomas or improve outcomes after chemotherapy. Neither epigallocatechin gallate nor artepillin C reduced the incidence of adenomas. Finally, fisetin seemed to improve the inflammatory status of patients under chemotherapy (5-fluorouracil). In summary, although certain polyphenols appear to exert some effect, their role in the prevention or treatment of CRC is inconclusive, and more clinical studies under more controlled conditions are needed.


Asunto(s)
Neoplasias Colorrectales , Polifenoles , Humanos , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/tratamiento farmacológico , Polifenoles/farmacología , Curcumina/farmacología , Curcumina/uso terapéutico , Adenoma/prevención & control , Adenoma/tratamiento farmacológico
2.
Int J Mol Sci ; 24(19)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37833878

RESUMEN

5-fluorouracil (5-FU) is an antineoplastic drug used to treat colorectal cancer, but it causes, among other adverse effects, diarrhea and mucositis, as well as enteric neuropathy, as shown in experimental animals. It might also cause neuropathic pain and alterations in visceral sensitivity, but this has not been studied in either patients or experimental animals. Cannabinoids have antimotility and analgesic effects and may alleviate 5-FU-induced adverse effects. Our aim was to evaluate the effects of the cannabinoid agonist WIN 55,212-2 on neuropathic and visceral pain induced by a non-diarrheagenic dose of 5-FU. Male Wistar rats received a dose of 5-FU (150 mg/kg, ip) and gastrointestinal motility, colonic sensitivity, gut wall structure and tactile sensitivity were evaluated. WIN 55,212-2 (WIN) was administered to evaluate its effect on somatic (50-100 µg ipl; 1 mg/kg, ip) and visceral (1 mg/kg, ip) sensitivity. The cannabinoid tetrad was used to assess the central effects of WIN (1 mg/kg, ip). 5-FU decreased food intake and body weight gain, produced mucositis and thermal hyperalgesia, but these effects were reduced afterwards, and were not accompanied by diarrhea. Tactile mechanical allodynia was also evident and persisted for 15 days. Interestingly, it was alleviated by WIN. 5-FU tended to increase colonic sensitivity whereas WIN reduced the abdominal contractions induced by increasing intracolonic pressure in both control and 5-FU-treated animals. Importantly, the alleviating effects of WIN against those induced by 5-FU were not accompanied by any effect in the cannabinoid tetrad. The activation of the peripheral cannabinoid system may be useful to alleviate neuropathic and visceral pain associated with antitumoral treatment.


Asunto(s)
Cannabinoides , Mucositis , Neuralgia , Dolor Visceral , Humanos , Ratas , Masculino , Animales , Ratas Wistar , Agonistas de Receptores de Cannabinoides/uso terapéutico , Dolor Visceral/tratamiento farmacológico , Dolor Visceral/etiología , Mucositis/tratamiento farmacológico , Fluorouracilo/efectos adversos , Benzoxazinas/farmacología , Benzoxazinas/uso terapéutico , Neuralgia/tratamiento farmacológico , Neuralgia/inducido químicamente , Cannabinoides/farmacología , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/inducido químicamente , Diarrea/tratamiento farmacológico
3.
Biomed Pharmacother ; 150: 112986, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35462333

RESUMEN

The role of spinal glia in the development and maintenance of chronic pain has become over the last years a subject of increasing interest. In this regard, toll-like receptor 4 (TLR4) signaling has been proposed as a major trigger mechanism. Hence, in this study we explored the implications of TLR4 inhibition in the periphery and primarily in the CNS, focusing on the impact this inhibition renders in pain development and glia activation in the dorsal horn in two models of pain. Making use of a synthetic cluster of differentiation 14 (CD14)/TLR4 antagonist, the effect of TLR4 blockade on tactile allodynia and heat hyperalgesia was evaluated in osteoarthritic and postoperative rat models. An in vitro parallel artificial membrane permeation assay was performed to determine the proneness of the drug to permeate the blood-brain barrier prior to systemic and central administration. Findings suggest a dominant role of peripheral TLR4 in the model of incisional pain, whilst both peripheral and central TLR4 seem to be responsible for osteoarthritic pain. That is, central and peripheral TLR4 may be differently involved in the etiopathology of diverse types of pain what potentially seems a promising approach in the management of pain.


Asunto(s)
Analgésicos , Dolor Crónico , Receptores de Lipopolisacáridos , Microglía , Receptor Toll-Like 4 , Analgésicos/farmacología , Animales , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/metabolismo , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Receptores de Lipopolisacáridos/antagonistas & inhibidores , Receptores de Lipopolisacáridos/metabolismo , Microglía/efectos de los fármacos , Neuroglía/efectos de los fármacos , Manejo del Dolor , Ratas , Ratas Sprague-Dawley , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/metabolismo
4.
Biomed Pharmacother ; 143: 112241, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34649363

RESUMEN

Flavonoids are plant bioactive compounds of great interest in nutrition and pharmacology, due to their remarkable properties as antioxidant, anti-inflammatory, antibacterial, antifungal and antitumor drugs. More than 5000 different flavonoids exist in nature, with a huge structural diversity and a plethora of interesting pharmacological properties. In this work, five flavonoids were tested for their potential use as antitumor drugs against three CRC cell lines (HCT116, HT-29 and T84). These cell lines represent three different stages of this tumor, one of which is metastatic. Xanthohumol showed the best antitumor activity on the three cancer cell lines, even better than that of the clinical drug 5-fluorouracil (5-FU), although no synergistic effect was observed in the combination therapy with this drug. On the other hand, apigenin and luteolin displayed slightly lower antitumor activities on these cancer cell lines but showed a synergistic effect in combination with 5-FU in the case of HTC116, which is of potential clinical interest. Furthermore, a literature review highlighted that these flavonoids show very interesting palliative effects on clinical symptoms such as diarrhea, mucositis, neuropathic pain and others often associated with the chemotherapy treatment of CRC. Flavonoids could provide a double effect for the combination treatment, potentiating the antitumor effect of 5-FU, and simultaneously, preventing important side effects of 5-FU chemotherapy.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Flavonoides/farmacología , Cuidados Paliativos , Antimetabolitos Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apigenina/farmacología , Neoplasias Colorrectales/patología , Sinergismo Farmacológico , Flavanonas/farmacología , Fluorouracilo/farmacología , Células HCT116 , Células HT29 , Humanos , Luteolina/farmacología , Propiofenonas/farmacología
5.
Front Pharmacol ; 12: 692970, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34366848

RESUMEN

Vincristine is an effective anticancer agent for treating leukemias, lymphomas, and other solid tumors. Vincristine's better-known severe side effects include bone marrow depression, hyponatremia, peripheral neuropathy, and gastrointestinal distress. In recent years, cardiovascular damage also has been described during vincristine treatments. However, the vascular toxicity induced by vincristine is little studied. The aim of the present is to evaluate whether these alterations remain after the suspension of chemotherapy treatment (sequelae) and the possible mechanisms involved in this vascular damage. Adult male Wistar rats were used. The animals were divided into four treatment groups: two groups of saline (0.9% NaCl; saline, sequelae saline) and two groups of vincristine (100 µg/kg; vincristine, sequelae vincristine). Saline or vincristine was administered intraperitoneally in two cycles of 5 days each, leaving a rest period between cycles of 2 days. The final cumulative vincristine dose administered was 1 mg/kg. Sequelae groups correspond to 2 weeks after stopping treatment with the antitumor agent. At the end of the different experimental protocols, cardiac and vascular functions were analyzed. Alterations in the expression of different proteins in the cardiovascular tissues were also investigated. Chronic treatment with vincristine did not produce significant changes in basal cardiac function but provoked significant endothelial dysfunction in the aorta and a significant decrease in the mesenteric contractile function. These cardiovascular functional alterations disappeared 2 weeks after the suspension of chemotherapy treatment. Vincristine treatment caused a significant increase in the expression of tumor necrosis factor-alpha (TNFα), endothelial and inducible nitric oxide synthases (eNOS and iNOS), and connexin 43 in cardiac tissue. In the aorta, the chronic treatment with vincristine caused a slight non-significant increase in TNFα expression, a significant increase in eNOS and iNOS, and a significant decrease in connexin 43. After 2 weeks of vincristine treatment (sequelae group), the expression of TNFα increased and eNOS and iNOS expressions disappeared, but a significant decrease in the expression of connexin 43 was still observed in the aorta. In mesenteric arteries, similar data to those found in the aorta were observed. In conclusion, chronic treatment with vincristine causes functional alterations in the vascular function of both conductance and resistance vessels and changes in the expressions of TNFα, eNOS, iNOS, and connexin 43 in cardiovascular tissues, implicating direct toxicity during its treatment. These functional alterations are transitory and disappear after the suspension of its treatment.

6.
Nutrients ; 13(6)2021 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-34070787

RESUMEN

Dietary modifications, including those affecting dietary fat and its fatty acid (FA) composition, may be involved in the development of brain-gut axis disorders, with different manifestations in males and females. Our aim was to evaluate the impact of three purified diets with different FA composition on the brain-gut axis in rats of both sexes. Male and female Wistar rats fed a cereal-based standard diet from weaning were used. At young adult age (2-3 months old), animals were divided into three groups and treated each with a different refined diet for 6 weeks: a control group fed on AIN-93G diet containing 7% soy oil (SOY), and two groups fed on AIN-93G modified diets with 3.5% soy oil replaced by 3.5% coconut oil (COCO) or 3.5% evening primrose oil (EP). Different brain-gut axis parameters were evaluated during 4-6 weeks of dietary intervention. Compared with SOY diet (14% saturated FAs, and 58% polyunsaturated FAs), COCO diet (52.2% saturated FAs and 30% polyunsaturated FAs) produced no changes in brain functions and minor gastrointestinal modifications, whereas EP diet (11.1% saturated FAs and 70.56% polyunsaturated FAs) tended to decrease self-care behavior and colonic propulsion in males, and significantly increased exploratory behavior, accelerated gastrointestinal transit, and decreased cecum and fecal pellet density in females. Changes in FA composition, particularly an increase in ω-6 polyunsaturated FAs, seem to facilitate the development of brain-gut axis alterations in a sex-dependent manner, with a relatively higher risk in females.


Asunto(s)
Encéfalo/fisiopatología , Dieta/métodos , Ácidos Grasos/administración & dosificación , Tracto Gastrointestinal/fisiopatología , Animales , Femenino , Masculino , Modelos Animales , Ratas , Ratas Wistar
7.
Molecules ; 25(18)2020 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-32962285

RESUMEN

Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells' activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms.


Asunto(s)
Suplementos Dietéticos , Ingestión de Alimentos/fisiología , Síndrome del Colon Irritable/metabolismo , Mastocitos/metabolismo , Dolor Abdominal/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Animales , Cannabidiol/metabolismo , Estreñimiento/metabolismo , Diarrea/metabolismo , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Flavonoides/química , Flavonoides/metabolismo , Heparina/metabolismo , Histamina/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Polifenoles/metabolismo , Calidad de Vida , Vitaminas/metabolismo
8.
Nutrients ; 13(1)2020 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-33383958

RESUMEN

Coffee is one of the most popular beverages consumed worldwide. Roasted coffee is a complex mixture of thousands of bioactive compounds, and some of them have numerous potential health-promoting properties that have been extensively studied in the cardiovascular and central nervous systems, with relatively much less attention given to other body systems, such as the gastrointestinal tract and its particular connection with the brain, known as the brain-gut axis. This narrative review provides an overview of the effect of coffee brew; its by-products; and its components on the gastrointestinal mucosa (mainly involved in permeability, secretion, and proliferation), the neural and non-neural components of the gut wall responsible for its motor function, and the brain-gut axis. Despite in vitro, in vivo, and epidemiological studies having shown that coffee may exert multiple effects on the digestive tract, including antioxidant, anti-inflammatory, and antiproliferative effects on the mucosa, and pro-motility effects on the external muscle layers, much is still surprisingly unknown. Further studies are needed to understand the mechanisms of action of certain health-promoting properties of coffee on the gastrointestinal tract and to transfer this knowledge to the industry to develop functional foods to improve the gastrointestinal and brain-gut axis health.


Asunto(s)
Encéfalo/efectos de los fármacos , Cafeína/farmacología , Café/química , Tracto Gastrointestinal/efectos de los fármacos , Antiinflamatorios , Antioxidantes/farmacología , Bebidas , Fibras de la Dieta , Microbioma Gastrointestinal , Tracto Gastrointestinal/patología , Humanos , Membrana Mucosa , Polímeros , Polifenoles
9.
J Food Biochem ; 43(12): e13062, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31571257

RESUMEN

Metabolic Syndrome (MS) is related to increased risk of early death due to cardiovascular complications, among others. Dietary intervention has been suggested as the safest and most cost-effective alternative for treatment of those alterations in patients with MS. The aim of this study was to investigate the effects of different egg white hydrolysates (HEW1 and HEW2) in obese Zucker rats, focus on the development of cardiovascular complications. Blood pressure, heart rate, basal cardiac function and vascular reactivity in aorta and mesenteric resistance arteries were evaluated. Reactive oxygen species production by dihydroethidium-emitted fluorescence, NOX-1 mRNA levels by qRT-PCR, angiotensin-converting enzyme activity by fluorimetry and kidney histopathology were also analysed. Both hydrolysates improve the endothelial dysfunction occurring in resistance arteries. Additionally, HEW2 reduced vascular oxidative stress. PRACTICAL APPLICATIONS: Egg white is a good source of bioactive peptides, some of them with high antioxidant activity. They may be used as functional foods ingredients and could serve as an alternative therapeutic option to decrease some Metabolic Syndrome-related complications. This study suggests that these hydrolysates could be an interesting non-pharmacological tool to control cardiovascular complications related to Metabolic Syndrome.


Asunto(s)
Antioxidantes/metabolismo , Aorta/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Clara de Huevo/química , Arterias Mesentéricas/efectos de los fármacos , Obesidad/complicaciones , Estrés Oxidativo/efectos de los fármacos , Hidrolisados de Proteína/metabolismo , Animales , Ratas , Ratas Zucker
10.
Nutrients ; 11(6)2019 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-31234581

RESUMEN

The bioaccessibility, metabolism, and excretion of lipids composing spent coffee grounds (SCGs) were investigated. An analysis of mycotoxins and an acute toxicity study in rats were performed for safety evaluation. Total fat, fatty acids, and diterpenes (cafestol and kahweol) were determined in SCGs and their digests obtained in vitro. A pilot repeated intake study was carried out in Wistar rats using a dose of 1 g SCGs/kg b.w. for 28 days. Fat metabolism was evaluated by analysis of total fat, cholesterol, and histology in liver. The dietary fiber effect of SCGs was measured radiographically. The absence of mycotoxins and toxicity was reported in SCGs. A total of 77% of unsaturated fatty acids and low amounts of kahweol (7.09 µg/g) and cafestol (414.39 µg/g) were bioaccessible after in vitro digestion. A significantly lower (p < 0.1) accumulation of lipids in the liver and a higher excretion of these in feces was found in rats treated with SCGs for 28 days. No lipid droplets or liver damage were observed by histology. SCGs acutely accelerated intestinal motility in rats. SCGs might be considered a sustainable, safe, and healthy food ingredient with potential for preventing hepatic steatosis due to their effect as dietary fiber with a high fat-holding capacity.


Asunto(s)
Coffea/metabolismo , Diterpenos/metabolismo , Ácidos Grasos/metabolismo , Semillas/metabolismo , Animales , Disponibilidad Biológica , Biotransformación , Coffea/toxicidad , Diterpenos/administración & dosificación , Ácidos Grasos/administración & dosificación , Heces/química , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Eliminación Intestinal , Hígado/metabolismo , Masculino , Proyectos Piloto , Ratas Wistar , Semillas/toxicidad , Factores de Tiempo
11.
Curr Med Chem ; 25(16): 1879-1908, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29210639

RESUMEN

BACKGROUND: Guanylate cyclase C (GC-C) receptor is a transmembrane receptor, predominantly expressed in intestinal epithelial cells, which is considered to play a main role in homeostasis and function of the digestive tract. The endogenous ligands for this receptor are the paracrine hormones uroguanylin and guanylin. Upon ligand binding, GC-C receptors increase cyclic guanosine monophosphate (cGMP) levels, regulating a variety of key cell-type specific processes such as chloride and bicarbonate secretion, epithelial cell growth, regulation of intestinal barrier integrity and visceral sensitivity. It has been suggested that GC-C acts as an intestinal tumor suppressor with the potential to prevent the initiation and progression of colorectal cancer. In fact, loss of ligand expression is a universal step in sporadic colorectal carcinogenesis. Interestingly, the role of GC-C is not limited to the digestive tract but it has been extended to several other systems such as the cardiovascular system, kidney, and the central nervous system, where it has been involved in a gut-hypothalamus endocrine axis regulating appetite. Objetive: In this review we summarize the physiology of the GC-C receptor and its ligands, focusing on newly developed drugs like linaclotide, and their suggested role to reverse/prevent the diseases in which the receptor is involved. CONCLUSION: Available data points toward a relationship between uroguanylin and guanylin and their receptor and pathological processes like gastrointestinal and renal disorders, colorectal cancer, obesity, metabolic syndrome and mental disorders among others. Recent pharmacological developments in the regulation of GC-receptor may involve further improvements in the treatment of relevant diseases.


Asunto(s)
GMP Cíclico/metabolismo , Guanilato Ciclasa/metabolismo , Receptores de Péptidos/metabolismo , Animales , Neoplasias Colorrectales/terapia , Hormonas Gastrointestinales/metabolismo , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Mucosa Intestinal/metabolismo , Enfermedades Renales/terapia , Péptidos Natriuréticos/metabolismo , Obesidad/terapia , Unión Proteica , Transporte de Proteínas , Transducción de Señal
12.
Pharmacol Rep ; 68(4): 816-26, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27267792

RESUMEN

Inflammatory bowel diseases (ulcerative colitis; Crohn's disease) are debilitating relapsing inflammatory disorders affecting the gastrointestinal tract, with deleterious effect on quality of life, and increasing incidence and prevalence. Mucosal inflammation, due to altered microbiota, increased intestinal permeability and immune system dysfunction underlies the symptoms and may be caused in susceptible individuals by different factors (or a combination of them), including dietary habits and components. In this review we describe the influence of the Western diet, obesity, and different nutraceuticals/functional foods (bioactive peptides, phytochemicals, omega 3-polyunsaturated fatty acids, vitamin D, probiotics and prebiotics) on the course of IBD, and provide some hints that could be useful for nutritional guidance. Hopefully, research will soon offer enough reliable data to slow down the spread of the disease and to make diet a cornerstone in IBD therapy.


Asunto(s)
Dieta , Suplementos Dietéticos , Enfermedades Inflamatorias del Intestino/dietoterapia , Humanos
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