Examinando por Autor "Abalo Delgado, Raquel"

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Alterations in the small intestinal wall and motor function after repeated cisplatin in rat.
(John Wiley & Sons Ltd, 2017) Uranga, José Antonio; García-Martínez, José Manuel; García-Jiménez, Custodia; Vera, Gema; Martín-Fontelles, María Isabel; Abalo Delgado, Raquel
Background: Gastrointestinal adverse effects occurring during cancer chemotherapy are well known and feared; those persisting once treatment has finished are relatively unknown. We characterized the alterations occurring in the rat small intestine, after repeated treatment with cisplatin. Methods: Male Wistar rats received saline or cisplatin (2 mg kg-1 week-1 , for 5 weeks, ip). Gastric motor function was studied non-invasively throughout treatment (W1-W5) and 1 week after treatment finalization (W6). During W6, upper gastrointestinal motility was also invasively studied and small intestinal samples were collected for histopathological and molecular studies. Structural alterations in the small intestinal wall, mucosa, submucosa, muscle layers, and lymphocytic nodules were histologically studied. Periodic acid-Schiff staining and immunohistochemistry for Ki-67, chromogranin A, and neuronal-specific enolase were used to detect secretory, proliferating, endocrine and neural cells, respectively. The expression of different markers in the tunica muscularis was analyzed by RT/qPCR. Key results: Repeated cisplatin induced motility alterations during and after treatment. After treatment (W6), the small intestinal wall showed histopathological alterations in most parameters measured, including a reduction in the thickness of circular and longitudinal muscle layers. Expression of c-KIT (for interstitial cells of Cajal), nNOS (for inhibitory motor neurons), pChAT, and cChAT (for excitatory motor neurons) increased significantly (although both ChATs to a lesser extent). Conclusions & inferences: Repeated cisplatin induces relatively long-lasting gut dysmotility in rat associated with important histopathological and molecular alterations in the small intestinal wall. In cancer survivors, the possible chemotherapy-induced histopathological, molecular, and functional intestinal sequelae should be evaluated.
Central Neurotoxicity of Chemotherapy
(Springer, 2023) López-Gómez, Laura; Abalo Delgado, Raquel; Vera, Gema
It is undeniable that the introduction of chemotherapeutic drugs has significantly increased the survival of cancer patients. In the recent years, new drugs are being developed for cancer treatment, but the use of classical chemotherapeutic agents are still essential. Unfortunately, most treatments, including both conventional antitumor drugs and newer therapies are associated with important side effects. For this reason, characterization and treatment of the adverse effects and sequelae associated with chemotherapy is an urgent clinical need. The mechanisms of action of these drugs produce the inhibition of division of cancer cells and the induction of apoptosis or other forms of cell death. But these mechanisms are also responsible for the appearance of unwanted side effects as other types of cells could be affected. Neurons are not fast-dividing cells, but they can be affected, and chemotherapy may induce neurotoxicity. The central nervous system is protected by the blood-brain barrier and has a low rate of cellular turnover, but it is still vulnerable to antitumoral drugs. Central side effects of chemotherapy are diverse and include encephalopathy, headache, seizures, cerebellar syndromes, visual loss, myelopathy, cerebrovascular complications and confusional states. In addition, chemotherapy has been correlated with mild deficits of memory and cognition, known as chemotherapy-induced cognitive impairment, ‘chemobrain’ or ‘chemofog’. These central toxicities could be the result from direct damage to neural tissues as well as from systemic causes. This chapter will review and compile main symptoms of central neurotoxicity described in patients treated with conventional chemotherapy. To facilitate understanding, main antitumoral classes have been summarized according to their mechanism of action.
Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat
(2023) Vera, Gema; López-Gómez, Laura; Girón, Rocio; Martín-Fontelles, María Isabel; Nurgali, Kulmira; Abalo Delgado, Raquel; Uranga Ocio, José Antonio
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 _g 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.
From the Gut to the Brain: The Role of Enteric Glial Cells and Their Involvement in the Pathogenesis of Parkinson's Disease.
(MPDI, 2024) Montalbán.Rodriguez, Alba; Abalo Delgado, Raquel; López-Gómez, Laura
The brain–gut axis has been identified as an important contributor to the physiopathology of Parkinson’s disease. In this pathology, inflammation is thought to be driven by the damage caused by aggregation of α-synuclein in the brain. Interestingly, the Braak’s theory proposes that α-synuclein misfolding may originate in the gut and spread in a “prion-like” manner through the vagus nerve into the central nervous system. In the enteric nervous system, enteric glial cells are the most abundant cellular component. Several studies have evaluated their role in Parkinson’s disease. Using samples obtained from patients, cell cultures, or animal models, the studies with specific antibodies to label enteric glial cells (GFAP, Sox-10, and S100β) seem to indicate that activation and reactive gliosis are associated to the neurodegeneration produced by Parkinson’s disease in the enteric nervous system. Of interest, Toll-like receptors, which are expressed on enteric glial cells, participate in the triggering of immune/inflammatory responses, in the maintenance of intestinal barrier integrity and in the configuration of gut microbiota; thus, these receptors might contribute to Parkinson’s disease. External factors like stress also seem to be relevant in its pathogenesis. Some authors have studied ways to reverse changes in EGCs with interventions such as administration of Tryptophan-2,3-dioxygenase inhibitors, nutraceuticals, or physical exercise. Some researchers point out that beyond being activated during the disease, enteric glial cells may contribute to the development of synucleinopathies. Thus, it is still necessary to further study these cells and their role in Parkinson’s disease.
Guanylate cyclase C: a current hot target, from physiology to pathology
(2018) Uranga, Jose Antonio; Castro, Marta; Abalo Delgado, Raquel
Abstract: 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.
Modulation of enteric glial cells by nutraceuticals during pathological processes
(Academic Press, 2024) López-Gómez, Laura; Abalo Delgado, Raquel
Nutraceuticals are bioactive compounds, found in natural sources generally used as food, that are recognized to exert beneficial effects useful to prevent or manage pathologies. The enteric glial cells reside in the gut wall and exert key roles in gastrointestinal tract functions. Importantly, these cells may be altered in response to different physiological conditions (aging, dietary changes), as well as in different local (inflammatory bowel diseases) and systemic inflammatory (rheumatoid arthritis, diabetes, ischemia/reperfusion, infections) and neurodegenerative (Parkinson’s, Alzheimer’s) diseases. As shown in this chapter, only a few preclinical studies, using cell cultures or animal models (rodents, pigs), have evaluated the effects of nutraceuticals on the enteric glial cells, including amino acids, peptides, omega-6 derivatives, cannabinoids and cannabinoid-like compounds, polyphenols, phytotherapy, and pre- and probiotics. Although still scarce, the obtained results are promising and should inspire new research in this area, even in clinical settings.
Nutraceuticals and Enteric Glial Cells
(MPDI, 2021) López-Gómez, Laura; Szymaszkiewicz, Agata; Zielinska, Marta; Abalo Delgado, Raquel
Nutraceuticals are products derived from food sources with health benefits in addition to their basic nutritional values. Many of them can positively affect and enhance the immune system, which is particularly pertinent in the current turbulent times of COVID-19. Not surprisingly, nutraceutical sales rose dramatically during the pandemic period. However, much research is still needed to understand how natural products interact with the immune system to clarify their chemical compositions, mechanisms of action, and effects on health and illnesses. This Special Issue provided an open forum for researchers to share their research findings in the growing interest in nutraceuticals. We received an overwhelming response with a total of 33 submissions, of which only nine original research papers and ten reviews were accepted after rigorous peer-review. The included articles research into natural substances of interest in nutraceuticals ranging from herbal medicine to vitamins to microbiota-derived metabolites. The investigated immune-related responses include cancer, neurological diseases, gastroenterological disorders, inflammatory conditions, and infections.
Nutraceuticals and Enteric Glial Cells
(MPDI, 2021-06-21) López-Gómez, Laura; Szymaszkiewicz, Agata; Zielińska, Marta; Abalo Delgado, Raquel
Until recently, glia were considered to be a structural support for neurons, however further investigations showed that glial cells are equally as important as neurons. Among many different types of glia, enteric glial cells (EGCs) found in the gastrointestinal tract, have been significantly underestimated, but proved to play an essential role in neuroprotection, immune system modulation and many other functions. They are also said to be remarkably altered in different physiopathological conditions. A nutraceutical is defined as any food substance or part of a food that provides medical or health benefits, including prevention and treatment of the disease. Following the description of these interesting peripheral glial cells and highlighting their role in physiological and pathological changes, this article reviews all the studies on the effects of nutraceuticals as modulators of their functions. Currently there are only a few studies available concerning the effects of nutraceuticals on EGCs. Most of them evaluated molecules with antioxidant properties in systemic conditions, whereas only a few studies have been performed using models of gastrointestinal disorders. Despite the scarcity of studies on the topic, all agree that nutraceuticals have the potential to be an interesting alternative in the prevention and/or treatment of enteric gliopathies (of systemic or local etiology) and their associated gastrointestinal conditions.
Nutraceuticals and peripheral glial cells: a possible link?.
(IMR Press, 2022-01-20) Szymaszkiewicz, Agata; López-Gómez, Laura; Zielińska, Marta; Abalo Delgado, Raquel
A nutraceutical is a food-derived molecule that provides medical or health benefits beyond its basic nutritional role, including the prevention and treatment of disease and its symptoms. In the peripheral nervous system, satellite glial cells are found in close relationship with neurons, mainly in peripheral sensory ganglia, but, compared with other glial cells, the relationship between these cells and nutraceuticals has received little attention. After describing satellite glial cells and their role and changes in physiology and pathology, we review the studies on the effects of nutraceuticals as modulators of their functions. Maybe due to the difficulties in selectively labeling these cells, only a few studies, performed mainly in rodent models, have analyzed nutraceutical effects, showing that N-acetylcysteine, curcumin, quercetin, osthole and resveratrol may palliate neuropathic pain through satellite glial cells-dependent pathways, namely antioxidant mechanisms and/or interference with purinergic signaling. Neither other conditions in which satellite glial cells are involved (visceral pain, nerve regeneration) nor other nutraceuticals or mechanisms of action have been studied. Although more preclinical and clinical research is needed, the available reports support the general notion that nutraceuticals may become interesting alternatives in the prevention and/or treatment of peripheral gliopathies and their associated conditions, including those affecting the satellite glial cells.
Preclinical models of irritable bowel syndrome.
(Academic Press, 2020) López-Gómez, Laura; Bagüés, Ana; Uranga Ocio, José Antonio; Abalo Delgado, Raquel
Irritable bowel syndrome (IBS) is a disorder of the gut-brain interaction, highly prevalent and impactful. Visceral hypersensitivity and alterations of colonic motility and defecation are definitory, but other features (increased intestinal permeability, anxiety, depression) also occur throughout the life of IBS patients. In this chapter, we will first review the different animal models that have been developed in an attempt to mimic IBS and its symptoms, which may vary according to the different underlying etiology. Thereafter, we will review the techniques and models that are used in vitro. Whereas in vivo models constitute the final preclinical step in the search of new effective and safe treatments, in vitro studies offer essential information on molecular mechanisms underlying the disease, which may open the gate to finding new treatment targets. Both approaches are therefore complementary and need to be considered for successful preclinical research on IBS.
Probiotics and Probiotic-like Agents against Chemotherapy-Induced Intestinal Mucositis: A Narrative Review
(MPDI, 2023) López-Gómez, Laura; Alcorta, Alexandra; Abalo Delgado, Raquel
Cancer chemotherapy has allowed many patients to survive, but not without risks derived from its adverse effects. Drugs, such as 5-fluorouracil, irinotecan, oxaliplatin, methotrexate, and others, as well as different drug combinations trigger intestinal mucositis that may cause or contribute to anorexia, pain, diarrhea, weight loss, systemic infections, and even death. Dysbiosis is a hallmark of chemotherapy-induced intestinal mucositis and diarrhea, and, therefore, strategies aimed at modulating intestinal microbiota may be useful to counteract and prevent those dreadful effects. This narrative review offers an overview of the studies performed to test the efficacy of probiotics and probiotic-like agents against chemotherapy-induced intestinal mucositis and its consequences. Microbiota modulation through the oral administration of different probiotics (mainly strains of Lactobacillus and Bifidobacterium), probiotic mixtures, synbiotics, postbiotics, and paraprobiotics has been tested in different animal models and in some clinical trials. Regulation of dysbiosis, modulation of epithelial barrier permeability, anti-inflammatory effects, modulation of host immune response, reduction of oxidative stress, or prevention of apoptosis are the main mechanisms involved in their beneficial effects. However, the findings are limited by the great heterogeneity of the preclinical studies and the relative lack of studies in immunocompromised animals, as well as the scarce availability of results from clinical trials. Despite this, the results accumulated so far are promising. Hopefully, with the aid of these agents, intestinal mucositis will be less impactful to the cancer patient in the near future.
The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?.
(MPDI, 2022-10-10) López-Gónez, Laura; Szymaszkiewicz, Agata; Zielinska, Marta; Abalo Delgado, Raquel
The enteric nervous system (ENS) is a part of the autonomic nervous system that intrinsically innervates the gastrointestinal (GI) tract. Whereas enteric neurons have been deeply studied, the enteric glial cells (EGCs) have received less attention. However, these are immunecompetent cells that contribute to the maintenance of the GI tract homeostasis through supporting epithelial integrity, providing neuroprotection, and influencing the GI motor function and sensation. The endogenous cannabinoid system (ECS) includes endogenous classical cannabinoids (anandamide, 2-arachidonoylglycerol), cannabinoid-like ligands (oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)), enzymes involved in their metabolism (FAAH, MAGL, COX-2) and classical (CB1 and CB2) and non-classical (TRPV1, GPR55, PPAR) receptors. The ECS participates in many processes crucial for the proper functioning of the GI tract, in which the EGCs are involved. Thus, the modulation of the EGCs through the ECS might be beneficial to treat some dysfunctions of the GI tract. This review explores the role of EGCs and ECS on the GI tract functions and dysfunctions, and the current knowledge about how EGCs may be modulated by the ECS components, as possible new targets for cannabinoids and cannabinoid-like molecules, particularly those with potential nutraceutical use.