Person: Ramos Alonso, Eva
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First Name
Eva
Last Name
Ramos Alonso
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Farmacología y Toxicología
Area
Toxicología
Identifiers
10 results
Search Results
Now showing 1 - 10 of 10
Item Potential of melatonin to reverse epigenetic aberrations in oral cancer: New findings(Experimental and Clinical Sciences Journal, 2023) Gil Martín, Emilio; Ramos Alonso, Eva; López Muñoz, Francisco; Egea, Javier; Romero Martínez, Manuel AlejandroIt is now an accepted principle that epigenetic alterations cause cellular dyshomeostasis and functional changes, both of which are essential for the initiation and completion of the tumor cycle. Oral carcinogenesis is no exception in this regard, as most of the tumors in the different subsites of the oral cavity arise from the cross-reaction between (epi)genetic inheritance and the huge challenge of environmental stressors. Currently, the biochemical machinery is put at the service of the tumor program, halting the cell cycle, triggering uncontrolled proliferation, driving angiogenesis and resistance to apoptosis, until the archetypes of the tumor phenotype are reached. Melatonin has the ability to dynamically affect the epigenetic code. It has become accepted that melatonin can reverse (epi)genetic aberrations present in oral and other cancers, suggesting the possibility of enhancing the oncostatic capacity of standard multimodal treatments by incorporating this indolamine as an adjuvant. First steps in this direction confirm the potential of melatonin as a countermeasure to mitigate the detrimental side effects of conventional first-line radiochemotherapy. This single effect could produce synergies of extraordinary clinical importance, allowing doses to be increased and treatments not to be interrupted, ultimately improving patients’ quality of life and prognosis. Motivated by the urgency of improving the medical management of oral cancer, many authors advocate moving from in vitro and preclinical research, where the bulk of melatonin cancer research is concentrated, to systematic randomized clinical trials on large cohorts. Recognizing the challenge to improve the clinical management of cancer, our motivation is to encourage comprehensive and robust research to reveal the clinical potential of melatonin in oral cancer control. To improve the outcome and quality of life of patients with oral cancer, here we provide the latest evidence of the oncolytic activity that melatonin can achieve by manipulating epigenetic patterns in oronasopharyngeal tissue.Item Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option?(Diseases, 2021) Romero Martínez, Manuel Alejandro; Ramos Alonso, Eva; López Muñoz, Francisco; Ríos, Cristóbal de los; Egea, Javier; Gil Martín, Emilio; Pita Pita, Rene; Torrado Durán, Juan José; Serrano López, Dolores Remedios; Juberias, AntonioBlister or vesicant chemical warfare agents (CWAs) have been widely used in different military conflicts, including World War I and the Iran-Iraq War. However, their mechanism of action is not fully understood. Sulfur and nitrogen mustard exert toxic effects not only through the alkylation of thiol-bearing macromolecules, such as DNA and proteins, but also produce free radicals that can develop direct toxic effects in target organs such as the eyes, skin, and respiratory system. The lack of effective treatments against vesicant CWAs-induced injury makes us consider, in this complex scenario, the use and development of melatonin-based therapeutic strategies. This multifunctional indoleamine could facilitate neutralization of the oxidative stress, modulate the inflammatory response, and prevent the DNA damage, as well as the long-term health consequences mediated by vesicant CWAs-induced epigenetic mechanisms. In this context, it would be essential to develop new galenic formulations for the use of orally and/or topically applied melatonin for the prophylaxis against vesicant CWAs, as well as the development of post-exposure treatments in the near future.Item Potential of Melatonin as Adjuvant Therapy of Oral Cancer in the Era of Epigenomics(Cancers, 2019) Capote-Moreno, Ana; Ramos Alonso, Eva; Egea, Javier; López-Muñoz, Francisco; Gil-Martín, Emilio; Romero Martínez, Manuel AlejandroThe wide variety of epigenetic controls available is rapidly expanding the knowledge of molecular biology even overflowing it. At the same time, it can illuminate unsuspected ways of understanding the etiology of cancer. New emerging therapeutic horizons, then, promise to overcome the current antitumor strategies need. The translational utility of this complexity is particularly welcome in oral cancer (OC), in which natural history is alarmingly disappointing due to the invasive and mutilating surgery, the high relapsing rate, the poor quality of life and the reduced survival after diagnosis. Melatonin activates protective receptor-dependent and receptor-independent processes that prevent tissue cancerisation and inhibit progressive tumor malignancy and metastasis. Related evidence has shown that melatonin pleiotropy encompasses gene expression regulation through all the three best-characterized epigenetic mechanisms: DNA methylation, chromatin modification, and non-coding RNA. OC has received less attention than other cancers despite prognosis is usually negative and there are no significant therapy improvements recorded in the past decade. However, a large research effort is being carried out to elucidate how melatonin´s machinery can prevent epigenetic insults that lead to cancer. In the light of recent findings, a comprehensive examination of biochemistry through which melatonin may reverse epigenetic aberrations in OC is an extraordinary opportunity to take a step forward in the clinical management of patients.Item Melatonin as Modulator for Sulfur and Nitrogen Mustard-Induced Inflammation, Oxidative Stress and DNA Damage: Molecular Therapeutics(Antioxidants, 2023) Ramos Alonso, Eva; Gil Martín, Emilio; Ríos, Cristóbal de los; Egea, Javier; López Muñoz, Francisco; Pita Pita, Rene; Juberías, Antonio; Torrado Durán, Juan José; Serrano López, Dolores Remedios; Reiter, Russel J.; Romero Martínez, Manuel AlejandroSulfur and nitrogen mustards, bis(2-chloroethyl)sulfide and tertiary bis(2-chloroethyl) amines, respectively, are vesicant warfare agents with alkylating activity. Moreover, oxidative/nitrosative stress, inflammatory response induction, metalloproteinases activation, DNA damage or calcium disruption are some of the toxicological mechanisms of sulfur and nitrogen mustard-induced injury that affects the cell integrity and function. In this review, we not only propose melatonin as a therapeutic option in order to counteract and modulate several pathways involved in physiopathological mechanisms activated after exposure to mustards, but also for the first time, we predict whether metabolites of melatonin, cyclic-3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine, and N1-acetyl-5-methoxykynuramine could be capable of exerting a scavenger action and neutralize the toxic damage induced by these blister agents. NLRP3 inflammasome is activated in response to a wide variety of infectious stimuli or cellular stressors, however, although the precise mechanisms leading to activation are not known, mustards are postulated as activators. In this regard, melatonin, through its anti-inflammatory action and NLRP3 inflammasome modulation could exert a protective effect in the pathophysiology and management of sulfur and nitrogen mustard-induced injury. The ability of melatonin to attenuate sulfur and nitrogen mustard-induced toxicity and its high safety profile make melatonin a suitable molecule to be a part of medical countermeasures against blister agents poisoning in the near future.- Project number: 190
Item Página web orientada a la evaluación in silico de nuevas sustancias con interés biológico (parte VI)(2023) Ramos Alonso, Eva; Marco Contelles, José Luis; Pita Pita, Rene; Rodríguez Martín, Abigail; Rodriguez Talavera, María; Egea, Javier; Paramo Muñoz, Ana; Ríos, Cristóbal de los; Romero Martínez, Manuel Alejandro; García Cantón, CarolinaEn la línea de las ediciones anteriores, los resultados obtenidos con el proyecto "INSILITOX" han sido muy positivos. Por esta razón, el equipo se ha propuesto continuar optimizando la página web añadiendo nuevos recursos que apoyen la formación de los estudiantes, tanto de Grado como de Posgrado, en este entorno multilingüe de aprendizaje virtual adaptativo. Item In Silico Prediction of the Toxic Potential of Neuroprotective Bifunctional Molecules Based on Chiral N-Propargyl-1,2-amino Alcohol Derivatives(Chemical Research in Toxicology, 2021) Ramos Alonso, Eva; Lajarín Cuesta, Rocío; Arribas, Raquel L.; García Frutos, Eva M.; González Lafuente, Laura; Egea, Javier; Ríos, Cristóbal de los; Romero Martínez, Manuel AlejandroN-Propargylamines are useful synthetic scaffolds for the synthesis of bioactive molecules, and in addition, they possess important pharmacological activities. We obtained several neuroprotective molecules, chiral 1,2-amino alcohols and 1,2-diamines, able to reduce by almost 70% the rotenone and oligomycin A-induced damage in SH-SY5Y cells. Furthermore, some molecules assessed also counteracted the toxicity evoked by the Ser/Thr phosphatase inhibitor okadaic acid. Before extrapolating these data to preclinical studies, we analyze the molecules through an in silico prediction system to detect carcinogenicity risk or other toxic effects. In light of these promising results, these molecules may be considered as a lead family of neuroprotective and relatively safe compounds.Item Redox Regulation of Microglial Inflammatory Response: Fine Control of NLRP3 Inflammasome through Nrf2 and NOX4(Antioxidants, 2023) Palomino Antolín, Alejandra; Decouty-Pérez, Céline; Farré Alins, Víctor; Narros Fernández, Paloma; López Rodríguez, Ana Belén; Álvarez Rubal, María; Valencia, Inés; López Muñoz, Francisco; Ramos Alonso, Eva; Cuadrado, Antonio; Casas, Ana I.; Romero Martínez, Manuel Alejandro; Egea, JavierThe role of inflammation and immunity in the pathomechanism of neurodegenerative diseases has become increasingly relevant within the past few years. In this context, the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the activation of inflammatory responses by promoting the maturation and secretion of pro-inflammatory cytokines such as interleukin-1β and interleukin-18. We hypothesized that the interplay between nuclear factor erythroid 2-related factor 2 (Nrf2) and NADPH oxidase 4 (NOX4) may play a critical role in the activation of the NLRP3 inflammasome and subsequent inflammatory responses. After priming mixed glial cultures with lipopolysaccharide (LPS), cells were stimulated with ATP, showing a significant reduction of IL1-β release in NOX4 and Nrf2 KO mice. Importantly, NOX4 inhibition using GKT136901 also reduced IL-1β release, as in NOX4 KO mixed glial cultures. Moreover, we measured NOX4 and NLRP3 expression in wild-type mixed glial cultures following LPS treatment, observing that both increased after TLR4 activation, while 24 h treatment with tert-butylhydroquinone, a potent Nrf2 inducer, significantly reduced NLRP3 expression. LPS administration resulted in significant cognitive impairment compared to the control group. Indeed, LPS also modified the expression of NLRP3 and NOX4 in mouse hippocampus. However, mice treated with GKT136901 after LPS impairment showed a significantly improved discrimination index and recovered the expression of inflammatory genes to normal levels compared with wild-type animals. Hence, we here validate NOX4 as a key player in NLRP3 inflammasome activation, suggesting NOX4 pharmacological inhibition as a potent therapeutic approach in neurodegenerative diseases.Item Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging(Antioxidants, 2023) Jiménez Carretero, Victoria; Ramos Alonso, Eva; Segura Chama, Pedro; Hernández, Adan; Baraibar, Andrés M.; Álvarez Merz, Iris; López Muñoz, Francisco; Egea, Javier; Solís, José M.; Romero Martínez, Manuel Alejandro; Hernández Guijo, Jesús M.The aim of this review is to explore the relationship between melatonin, free radicals, and non-excitatory amino acids, and their role in stroke and aging. Melatonin has garnered significant attention in recent years due to its diverse physiological functions and potential therapeutic benefits by reducing oxidative stress, inflammation, and apoptosis. Melatonin has been found to mitigate ischemic brain damage caused by stroke. By scavenging free radicals and reducing oxidative damage, melatonin may help slow down the aging process and protect against age-related cognitive decline. Additionally, non-excitatory amino acids have been shown to possess neuroprotective properties, including antioxidant and anti-inflammatory in stroke and aging-related conditions. They can attenuate oxidative stress, modulate calcium homeostasis, and inhibit apoptosis, thereby safeguarding neurons against damage induced by stroke and aging processes. The intracellular accumulation of certain non-excitatory amino acids could promote harmful effects during hypoxia-ischemia episodes and thus, the blockade of the amino acid transporters involved in the process could be an alternative therapeutic strategy to reduce ischemic damage. On the other hand, the accumulation of free radicals, specifically mitochondrial reactive oxygen and nitrogen species, accelerates cellular senescence and contributes to age-related decline. Recent research suggests a complex interplay between melatonin, free radicals, and non-excitatory amino acids in stroke and aging. The neuroprotective actions of melatonin and non-excitatory amino acids converge on multiple pathways, including the regulation of calcium homeostasis, modulation of apoptosis, and reduction of inflammation. These mechanisms collectively contribute to the preservation of neuronal integrity and functions, making them promising targets for therapeutic interventions in stroke and age-related disorders.Item QuinoxalineTacrine QT78, a Cholinesterase Inhibitor as a Potential Ligand for Alzheimer’s Disease Therapy(Molecules, 2019) Ramos Alonso, Eva; Palomino-Antolín, Alejandra; Bartolini, Manuela; Iriepa, Isabel; Moraleda, Ignacio; Diez-Iriepa, Daniel; Samadi, Abdelouahid; Cortina, Carol V.; Chioua, Mourad; Egea, Javier; Romero Martínez, Manuel Alejandro; Marco-Contelles, JoséWe report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 μM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 ± 1.3 μM; IC50 (hBuChE) = 6.79 ± 0.33 μM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer’s disease.Item Redox Regulation of Microglial Inflammatory Response: Fine Control of NLRP3 Inflammasome through Nrf2 and NOX4(Antioxidants, 2023) Palomino Antolín, Alejandra; Decouty-Pérez, Céline; Farré Alins, Víctor; Narros Fernández, Paloma; López Rodríguez, Ana Belén; Álvarez Rubal, María; Valencia, Inés; López-Muñoz, Francisco; Ramos Alonso, Eva; Cuadrado, Antonio; Casas, Ana I.; Romero Martínez, Manuel Alejandro; Egea, JavierThe role of inflammation and immunity in the pathomechanism of neurodegenerative diseases has become increasingly relevant within the past few years. In this context, the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the activation of inflammatory responses by promoting the maturation and secretion of pro-inflammatory cytokines such as interleukin-1β and interleukin-18. We hypothesized that the interplay between nuclear factor erythroid 2-related factor 2 (Nrf2) and NADPH oxidase 4 (NOX4) may play a critical role in the activation of the NLRP3 inflammasome and subsequent inflammatory responses. After priming mixed glial cultures with lipopolysaccharide (LPS), cells were stimulated with ATP, showing a significant reduction of IL1-β release in NOX4 and Nrf2 KO mice. Importantly, NOX4 inhibition using GKT136901 also reduced IL-1β release, as in NOX4 KO mixed glial cultures. Moreover, we measured NOX4 and NLRP3 expression in wild-type mixed glial cultures following LPS treatment, observing that both increased after TLR4 activation, while 24 h treatment with tert-butylhydroquinone, a potent Nrf2 inducer, significantly reduced NLRP3 expression. LPS administration resulted in significant cognitive impairment compared to the control group. Indeed, LPS also modified the expression of NLRP3 and NOX4 in mouse hippocampus. However, mice treated with GKT136901 after LPS impairment showed a significantly improved discrimination index and recovered the expression of inflammatory genes to normal levels compared with wild-type animals. Hence, we here validate NOX4 as a key player in NLRP3 inflammasome activation, suggesting NOX4 pharmacological inhibition as a potent therapeutic approach in neurodegenerative diseases.