Person:
Ramos Alonso, Eva

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

Identifiers

Full item page

Search Results

Now showing 1 - 10 of 26

Plasma disposition and tissue depletion of chlortetracycline in the food producing animals, chickens for fattening
(Food and Chemical Toxicology, 2012) Anadón Navarro, Arturo Ramón; Gamboa, Felipe; Martínez Caballero, María Aranzazu; Castellano Santos, Víctor Jesús; Martínez Caballero, Marta; Ares Lombán, Irma; Ramos Alonso, Eva; Suárez, Frank H.; Martínez Larrañaga, María Rosa
Chickens were used to investigate plasma disposition of chlortetracycline after single IV (15 mg/kg) and multiple oral administration (60 mg/kg, 5 days) and residue depletion of chlortetracycline after multiple oral doses (60 mg/kg, 5 days). Plasma and tissue samples were analyzed by HPLC. Mean elimination half-lives in plasma were 7.96 and 13.15 h after IV and multiple oral administration. Maximum plasma concentration was 4.33 lg/ml and the interval from oral administration until maximal concentration was 1.79 h. Oral bioavailability was 17.76%. After multiple oral dose, mean kidney, liver and muscle tissue concentrations of chlortetracycline + 4-epi-chlortetracycline of 835.3, 192.7, and 126.3 ug/kg, respectively, were measured 1 day after administration of the final dose of chlortetracycline. Chlortetracycline residues were detected in kidney and liver (205.4 and 81.7 ug/kg, respectively), but not in muscle, 3 days after the end of chlortetracycline treatment. The mean chlortetracycline + 4-epi-chlortetracycline concentrations were below LOQ at 3 and 5 days after cessation of medication in muscle and liver, respectively. A withdrawal time of 3 days was necessary to ensure that the chlortetracycline residues were less than the maximal residue limits (MRLs) established by the European Union (100, 300, and 600 ug/kg in muscle, liver, and kidney, respectively).
Guía de prácticas y seminarios de Fundamentos de Toxicología
(2021) Ramos Alonso, Eva; Pino Sans, Javier Del; Romero Martínez, Manuel Alejandro; Díaz Plaza, María Jesús; Frejo Moya, María Teresa; Moyano-Cires Ivanoff, Paula Viviana
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 Alejandro
It 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.
Toxicological and pharmacological evaluation, antioxidant, ADMET and molecular modeling of selected racemic chromenotacrines {11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ols} for the potential prevention and treatment of Alzheimer’s disease
(European Journal of Medicinal Chemistry, 2014) Oset Gasque, María Jesús; González Prieto, María Pilar; Pérez Peña, Javier; García Font, Nuria; Romero Martínez, Manuel Alejandro; Pino Sans, Javier Del; Ramos Alonso, Eva; Hadjipavlou-Litina, Dimitra; Soriano, Elena; Chioua, Mourad; Samadi, Abdelouahid; Raghuvanshi, Dushyant S.; Singh, Krishna N.; Marco Contelles, José
The pharmacological analysis of racemic chromenotacrines (CT) 1e7, bearing the 11-amino-12-aryl-8,9,10,12-tetrahydro-7H-chromeno[2,3-b]quinolin-3-ol ring skeleton, in a series of experiments targeted to explore their potential use for the treatment of Alzheimer’s disease (AD), is reported. The toxicological evaluation showed that among all these chromenotacrines, CT6 is much less hepatotoxic than tacrine in a range of concentrations from 1 to 300 mM, measured as cell viability in HepG2 cells. Moreover, CT6 did not significantly increase lactate dehydrogenase, aspartate transaminase, and alanine transaminase release in HepG2 cells. Besides,CT6treatment exerts a high protective effect against thelipid peroxidationinduced after H2O2-treated SHSY5Y cells, in a concentration-dependent manner. CT6 showed an excellent antioxidant profile in the AAPH test, and protects against the decrease in cell viability induced by respiratory chain inhibitors (Oligomicyn A/Rotenone)and NO donors in neuronal cultures. This effect could be due to a mixed antiapoptotic and antinecrotic neuroprotective effect at low and intermediate CT6 concentrations, respectively. CT1-7 are potent and selective inhibitors of EeAChE in the submicromolar range. CT3 [IC50 (EeAChE) ¼ 0.007 0.003 mM], and CT6 [IC50 (EeAChE) ¼ 0.041 0.001 mM] are the most potent AChE inhibitors. Kinetic studies on the non-toxic chromenotacrine CT6 showed that this compound behaves as a non-competitive inhibitor (Ki ¼ 0.047 0.003 mM),indicating that CT6 binds at the peripheral anionic site, a fact confirmed by molecular modeling analysis. In silico ADMET analysis showed also that CT6 should have a moderate BBB permeability. Consequently, non-toxic chromenotacrine CT6can be considered as an ttractivemultipotent molecule for the potential treatment of AD.
Fipronil sulfone induced higher cytotoxicity than fipronil in SH-SY5Y cells: Protection by antioxidants
(Toxicology Letters, 2016) Romero Martínez, Manuel Alejandro; Ramos Alonso, Eva; Ares Lombán, Irma; Castellano Santos, Víctor Jesús; Martínez Caballero, Marta; Martínez Larrañaga, María Rosa; Anadón Navarro, Arturo Ramón; Martínez Caballero, María Aranzazu
Fipronil is a broad spectrum insecticide from the phenyl pyrazole family, which targets GABA receptor. Limited information is available about the metabolite fipronil sulfone cytotoxic actions. This study examined in vitro neurotoxicity of fipronil and fipronil sulfone and evaluated Trolox (vitamin E analog) (0.3, 1μM), N-acetyl-cysteine (0.5, 1mM), melatonin (0.1, 1μM) and Tempol (superoxide dismutase analog) (0.3, 0.5mM) protective role in SH-SY5Y cells. MTT and LDH assays were carried out to assess the cytotoxicity of fipronil and fipronil sulfone at 3-100μM concentrations. Fipronil sulfone was more toxic than fipronil. Tempol showed the best neuroprotectant profile against fipronil (50 and 150μM) and fipronil sulfone (3 and 10μM) reaching control levels. Fipronil (100μM) and fipronil sulfone (3μM) treatments induced a 4.7- and 5-fold increases in lipid peroxides measured as malondialdehyde (MDA) and a 2.2- and 2.0-fold increases in the levels of nitric oxide (NO). These results suggest that oxidative stress observed may be one of the major mechanisms of fipronil-induced neurotoxicity and it may be attributed in part to fipronil disposition and metabolism. Our results led us postulate that metabolite fipronil sulfone might be responsible for the fipronil-induced toxicity rather than fipronil itself.
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.
Project number: PMICD302/23-24
Página web orientada a la evaluación toxicológica “in silico” de nuevas sustancias con interés biológico 2023-24
(2024) Ramos Alonso, Eva; Romero Martínez, Manuel Alejandro; De Los Ríos Salgado, Cristóbal; Egea Máiquez, Francisco Javier; García Cantón, Carolina; Pita Pita, Rene; Rodríguez Martín, Abigail; Rodríguez Talavera, María; Suero Martín, Alba; Ramos Alonso, Eva
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 Alejandro
The 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.
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 Alejandro
Sulfur 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.
Guía de Prácticas de Laboratorio y seminarios de Toxicología Veterinaria
(2021) Ramos Alonso, Eva; Pino Sans, Javier Del; Romero Martínez, Manuel Alejandro; Díaz Plaza, María Jesús; Frejo Moya, María Teresa; Moyano-Cires Ivanoff, Paula Viviana