Person:
Ramos Alonso, Eva

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First Name
Eva
Last Name
Ramos Alonso
URI
https://hdl.handle.net/20.500.14352/80441
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Farmacología y Toxicología
Area
Toxicología
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2021 - 20232
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Author: Egea, Javier × Subject: 615.9 ×

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    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, Antonio
    Blister 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.
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    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, Javier
    The 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.