Toxicology and Population Risk Group

Responsible Dr. Javier Esteban Mozo

 

RESEARCH SUMMARY

The main objective of the group is the study of mechanisms of toxicity and both genetic and environmental modifying factors, that affect the response of the populations exposed to environmental pollutants, such as persistent organic compounds and endocrine disruptors, drugs and addictive substances.

tox poblacional portada

Image taken from Suylen Galbán Velázquez et al. (2021). Environmental Research 195:110764. https://doi.org/10.1016/j.envres.2021.110764

 

RESEARCH LINES

 

Line 1: Evaluation of biomarker response in biological samples from human populations exposed to environmental contaminants

Human populations are exposed to a large number of chemicals in occupational and environmental settings. Environmental pollutants that persist in the environment, either by continuous emission or by slow biodegradation, are ubiquitously distributed in the form of complex mixtures, accumulate in living organisms and cause toxicity.

The search for early indicators is useful for detecting the development of pathological states that constitute serious public health problems, such as obesity, diabetes, cardiovascular diseases, metabolic syndrome, immune system alterations, cancer, as well as reproductive and developmental disorders derived from exposure to chemical substances. 

Line 2: Evaluation of molecular biomarkers in patients treated with psychotropic drugs predisposing to metabolic syndrome

The presence of multiple factors involved in the pathogenesis, as well as genetic predisposition and lifestyle habits, make it difficult to clarify the mechanisms that determine the course of endocrine disorders such as metabolic syndrome in the general population.

Therefore, the study in patients under medical control who receive a treatment that predisposes, as a side effect, to the development of metabolic syndrome, allows us to obtain information about biomarkers linked to mechanisms of action, such as key elements of the retinoid system, and others linked to individual susceptibility factors, such as paraoxonase. It is proposed that the determination of such biomarkers would facilitate the identification of risk groups.

S. Galbán-Velázquez, J. Esteban, G. Çakmak, F. Artacho-Cordón, J. León, J. Barril, F. Vela-Soria, P. Martin-Olmedo, M. F Fernandez, M. C. Pellín, J. P Arrebola
Associations of persistent organic pollutants in human adipose tissue with retinoid levels and their relevance to the redox microenvironment
Environmental Research (2021).

 

R. Pohjanvirta, I. Karppinen, S. Galbán-Velázquez, J. Esteban, H. Håkansson, S. Sankari, J. Lindén
Effects of a high-fat diet and global aryl hydrocarbon receptor deficiency on energy balance and liver retinoid status in male Sprague-Dawley rats
The Journal of Nutritional Biochemistry, Volume 95 (2021).

 

M. Herlin, I. Sánchez-Pérez, J. Esteban, M. Korkalainen, X. Barber, M.A.J. Finnilä, G. Hamscher, B. Joseph, M. Viluksela, H. Håkansson
Bone toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the retinoid system: A causality analysis anchored in osteoblast gene expression and mouse data
Reproductive Toxicology 105:25-43 (2021).

 

S. Alarcón, J. Esteban, R. Roos, P. Heikkine, I. Sánchez-Pérez, A. Adamsson, J. Toppari, A. Koskela, M.A.J. Finnilä, J Tuukkanen, M Herlin, G Hamscher, H.A. Leslie, M. Korkalainen, K Halldin, D. Schrenk, H. Håkansson, M. Viluksela
Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2′,3,4,4′,5,5′-heptachlorobiphenyl (PCB 180): A postnatal follow-up study in rats
Reproductive Toxicology 102:109-127 (2021).

 

J. Esteban, I. Sánchez-Pérez, G. Hamscher, H. M Miettinen, M. Korkalainen, M. Viluksela, R. Pohjanvirta, H. Håkansson
Role of aryl hydrocarbon receptor (AHR) in overall retinoid metabolism: Response comparisons to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure between wild-type and AHR knockout mice
Reproductive Toxicology 101:33-49 (2021).

 

J. Esteban, M. Serrano-Maciá, I. Sánchez-Pérez, P. Alonso-Magdalena, M. C. Pellín, M. García-Arévalo, Á. Nadal, J. Barril
In utero exposure to bisphenol-A disrupts key elements of retinoid system in male mice offspring
Food and Chemical Toxicology (2019).

 

S. Mahiout, J. Lindén, J. Esteban, I. Sánchez-Pérez, S. Sankari, L. Pettersson, H. Håkansson, R. Pohjanvirta
Toxicological characterisation of two novel selective aryl hydrocarbon receptor modulators in Sprague-Dawley rats
Toxicology and Applied Pharmacology (2017).

 

J. Esteban, L. E. Elabbas, D. Borg, M. Herlin, A. Åkesson, X. Barber, G. Hamscher, H. Nau, W. J. Bowers, J. S. N., M. Viluksela, H. Håkanssona
Gestational and lactational exposure to the polychlorinated biphenyl mixture Aroclor 1254 modulates retinoid homeostasis in rat offspring
Toxicology Letters (2014).

 

M. Viluksela, P. Heikkinen, L. T. M. van der Ven, F. Rendel, R. Roos, J. Esteban,M. Korkalainen,S. Lensu,H. M. Miettinen, K. Savolainen, S. Sankari, H. Lilienthal, A. Adamsson, J. Toppari, M. Herlin, M. Finnilä, J. Tuukkanen, H. A. Leslie, T. Hamers, G. Hamscher, L. Al-Anati, U. Stenius, K. Dervola, I. Bogen, F. Fonnum, P. L. Andersson, D. Schrenk, K. Halldin, H. Håkansson
Toxicological profile of ultrapure 2,2′,3,4,4′,5,5′- heptachlorbiphenyl (PCB 180) in adult rats
PLoS ONE (2014).

 

C. López-Granero, D. Cardona, E. Giménez, R. Lozano, J. Barril, M. Aschner, F. Sánchez-Santed, F. Cañadas
Comparative study on short- and long-term behavioral consequences of organophosphate exposure: relationship to AChE mRNA expression
Neurotoxicology (2014).

 

Contrato para la realización del trabajo «Evaluación de la respuesta del marcador de inflamación RBP4 en suero de humanos expuestos a contaminantes ambientales que causan estrés oxidativo. Funding agency: Fundación para la Investigación Biosanitaria de Andalucía Oriental. Duration: 03/12/2020 – 02/08/2021.
PI: Javier Esteban


Contrato para la realización del trabajo “Comparación del perfil retinoide en ratas con alelos silvestre y noqueado del gen AhR”. Funding agency: Helsingin Yliopisto. Duration: 20/12/2018 – 19/12/2019.
PI: Javier Esteban


Contrato para la realización del trabajo “Determinación de compuestos retinoides en muestras de animales de experimentación tratados con contaminantes orgánicos persistentes”. Funding agency: Karolinska Institutet. Duration: 10/03/2014 – 09/12/2018.
PI: Javier Esteban


Contrato para la realización del trabajo “Determinación de compuestos retinoides en muestras de animales de experimentación tratados con agonistas AhR”. Funding agency: Helsingin Yliopisto. Duration: 19/05/2016 – 18/05/2017.
PI: Javier Esteban


Raising the awareness of healthy food and healthy eating among children. Funding agency: European Commission 2011-1-TR1-LEO04-27384. Duration: 01/08/2011 – 31/07/2013.
PI:Javier Esteban


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Contrato para la realización del trabajo “Evaluación de la respuesta del marcador de inflamación RBP4 en suero de humanos expuestos a contaminantes ambientales que causan estrés. Funding agency: FIBAO1.20T. Duration: 03/12/2020 – 03/2/2021.
PI: Javier Esteban


Raising the awareness of healthy food and healthy eating among children. Funding agency: European Commission 2011-1-TR1-LEO04-27384. Duration: 01/08/2011 – 31/07/2013.
PI: Javier Esteban


Disruption of the retinoid system by non-dioxin-like polychlorinated byphenyls present in food. Funding agency: Proyectos BANCAJA-UMH. Duration: 01/01/2009 – 31/12/2010.
PI: Javier Esteban


Efectos neurotoxicos a largo plazo de la exposicion a compuestos organofosforados: Implicacion de nuevas variantes de las enzimas ache y otras carboxilesterasas. Funding agency: Becas y ayudas para el fomento de la investigacion cientifica y el desarrollo tecnologico e\gv07/158. Duration: 01/01/2007 – 31/12/2008.
PI: José Ramón Barril


Influencia de la comedicacion de antirretrovirales y psicofarmacos en los niveles plasmaticos. Funding agency: Conselleria de sanidad. Duration: 18/02/2005 – 31/12/2005.
PI: Javier Esteban

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Grupo científico de expertos de la Organización para la Cooperación y el Desarrollo Económicos. OCDE. 2021. No. 343 Detailed review paper on the Retinoid System. Publications on Testing and Assessment. European Commission Framework Contract ENV.A.3/FRA/2014/0029 on Implementation of the Community Strategy on Endocrine Disruptors: Supporting the development of the OECD detailed review paper on the retinoid system.

Job title: Alteration of the retinoid system due to exposure to xenobiotics.
Within the Program: PhD in Bioengineering (RD 1393/2007)
Project type: Doctoral Thesis
Entity: Universidad Miguel Hernández
Student: Sanchez Pérez, Ismael
Qualification obtained: Sobresaliente Cum Laude
Date: 22/09/2017

Job title: Toxicity of brominated flame retardants with focus on retinoid system disturbances
Within the Program : Karolinska Institutet
Project type: Doctoral Thesis
Entity: Universidad Miguel Hernández
Student: Sabina Litens Karlsson
Qualification obtained: Sobresaliente Cum Laude
Date: 08/06/2015

Name of the exhibition: Raising the awareness of healthy food and healthy eating among children
Authors: Esteban, J.; Barril, J.; E. Garcia Garcia; Pellín, M.C.
Forum where it is exposed: HEALTHY FOOD – EUROPEAN COMMISSION
Start date: 01/08/2011
Available atAlimentación saludable para una vida sana. ISBN 978-84-16024-02-5