Advanced search


Knowledge area




700 results, page 1 of 10

Purine nucleoside phosphorylase and the enzymatic antioxidant defense system in breast milk from women with different levels of arsenic exposure

Purina nucleósido fosforilasa y el sistema de defensa antioxidante enzimático en leche materna de mujeres con diferentes niveles de exposición a arsénico

RAMON GAXIOLA ROBLES VANESSA LABRADA MARTAGON OSCAR KURT BITZER QUINTERO TANIA ZENTENO SAVIN LIA CELINA MENDEZ RODRIGUEZ (2015)

"Purine nucleoside phosphorylase (PNP) is an ubiquitous enzyme which plays an important role in arsenic (As) detoxification. As is a toxic metalloid present in air, soil and water; is abundant in the environment and is readily transferred along the trophic chain, being found even in human breast milk. Milk is the main nutrient source for the growth and development of neonates. Information on breast milk synthesis and its potential defense mechanism against As toxicity is scarce. In this study, PNP and antioxidant enzymes activities, as well as glutathione (GSH) and total arsenic (TAs) concentrations, were quantified in breast milk samples. PNP, superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) activities and GSH concentration were determined spectrophotometrically; TAs concentration ([TAs]) was measured by atomic absorption spectrometry. Data suggest an increase in PNP activity (median = 0.034 U mg protein-1) in the presence of TAs (median = 1.16 g L-1). To explain the possible association of PNP activity in breast milk with the activity of the antioxidant enzymes as well as with GSH and TAs concentrations, generalized linear models were built. In the adjusted model, GPx and GR activities showed a statistically significant (p<0.01) association with PNP activity. These results may suggest that PNP activity increases in the presence of TAs as part of the detoxification mechanism in breast milk."

"Purina nucleósido fosforilasa (PNP) es una enzima ubicua que desempeña un papel importante en la desintoxicación del arsénico (As). As es un metaloide tóxico presente en el aire, el suelo y el agua; es abundante en el medio ambiente y se transfiere fácilmente a lo largo de la cadena trófica, encontrándose incluso en la leche materna humana. Información sobre la síntesis de la leche materna y su potencial mecanismo de defensa contra tóxicos es escasa. En este estudio, se cuantificó la actividad de PNP y de las enzimas antioxidantes así como la concentración de glutatión (GSH) y de arsénico total ([TAs]) en muestras de leche materna. La actividad de PNP, superóxido dismutasa (SOD), catalasa (CAT), glutatión S-transferasa (GST), glutatión peroxidasa (GPx), glutatión reductasa (GR) y la concentración de GSH se determinaron por espectrofotometría; la [TAs] se midió por espectrometría de absorción atómica. Los datos sugieren un incremento en la actividad de PNP (mediana= 0.034 U mg proteína-1) con la presencia de TAs (mediana= 1.16 g L-1). Para explicar la posible asociación de la actividad de las enzimas antioxidantes y la concentración de GSH, así como [TAs], con la actividad de PNP en la leche materna, se construyeron modelos lineales generalizados. En el modelo ajustado, la actividad de GPx y GR presentó una asociación estadística (p<0.01) con la actividad de PNP. Los resultados pueden sugerir que la actividad de PNP aumenta con la presencia de TAs como parte del mecanismo de desintoxicación en la leche materna."

Article

Arsenic, Breast milk, Generalized linear model, Oxidative stress, Purine nucleoside phosphorylase Estrés oxidativo, Leche maternal, Modelo lineal generalizado, Purina nucleósido fosforilasa BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA BIOQUÍMICA ENZIMOLOGIA

Interaction between mercury (Hg), arsenic (As) and selenium (Se) affects the activity of glutathione S-transferase in breast milk; possible relationship with fish and shellfish intake

EFECTO DE LA INTERACCIÓN ENTRE MERCURIO (Hg), ARSÉNICO (As) Y SELENIO (Se) EN LA ACTIVIDAD DE GLUTATIÓN S-TRANSFERASA EN LECHE MATERNA; POTENCIAL RELACIÓN CON EL CONSUMO DE PESCADOS Y MARISCOS

RAMON GAXIOLA ROBLES VANESSA LABRADA MARTAGON ALFREDO DE JESUS CELIS DE LA ROSA BAUDILIO ACOSTA VARGAS LIA CELINA MENDEZ RODRIGUEZ TANIA ZENTENO SAVIN (2014)

"Breast milk is regarded as an ideal source of nutrients for the growth and development of neonates, but it can also be a potential source of pollutants. Mothers can be exposed to different contaminants as a result of their lifestyle and environmental pollution. Mercury (Hg) and arsenic (As) could adversely affect the development of fetal and neonatal nervous system. Some fish and shellfish are rich in selenium (Se), an essential trace element that forms part of several enzymes related to the detoxification process, including glutathione S-transferase (GST). The goal of this study was to determine the interaction between Hg, As and Se and analyze its effect on the activity of GST in breast milk. Milk samples were collected from women between day 7 and 10 postpartum. The GST activity was determined spectrophotometrically; total Hg, As and Se concentrations were measured by atomic absorption spectrometry. To explain the possible association of Hg, As and Se concentrations with GST activity in breast milk, generalized linear models were constructed. The model explained 44% of the GST activity measured in breast milk. The GLM suggests that GST activity was positively correlated with Hg, As and Se concentrations. The activity of the enzyme was also explained by the frequency of consumption of marine fish and shellfish in the diet of the breastfeeding women."

"La leche materna es considerada como una fuente ideal de nutrientes para el crecimiento y el desarrollo de los recién nacidos, pero también puede ser una fuente potencial de contaminantes. Las madres pueden estar expuestas a diversos contaminantes como resultado de su estilo de vida y de la contaminación ambiental. Mercurio (Hg) y arsénico (As) pueden afectar negativamente el desarrollo del sistema nervioso fetal y neonatal. Algunos peces y mariscos son ricos en selenio (Se), un oligoelemento esencial que forma parte de diversas enzimas relacionadas con el proceso de desintoxicación, incluyendo glutatión S-transferasa (GST). El objetivo de este estudio fue determinar la interacción entre Hg, As y Se, así como analizar su efecto sobre la actividad de GST en la leche materna. Muestras de leche materna fueron obtenidas entre los días 7 y 10 después del parto. La actividad de la GST fue determinada espectrofotométricamente. Las concentraciones totales de Hg, As y Se fueron medidas por espectrometría de absorción atómica. Para explicar la posible asociación de las concentraciones de Hg, As y Se con la actividad de la GST en la leche materna, se construyeron modelos lineales generalizados. El modelo explicó el 44% de la actividad de GST medida en leche materna. El MLG sugiere que la actividad de GST se correlacionó positivamente con las concentraciones de Hg, As y Se. La actividad de la enzima se explica también por la frecuencia de consumo de peces marinos y mariscos en la dieta de las mujeres que se encuentran en periodo de lactancia."

Article

Breast milk, Generalized linear model, Glutatione S-transferase, Oxidative stress, Trace elements Leche materna, Modelos lineales generalizados, Glutation S-transferasa, Estrés oxidativo, Elementos traza BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA BIOQUÍMICA RADICALES LIBRES

Defensas antioxidantes en leche materna en relación al número de gestas y a la edad de las madres

PATRICIA CAROLINA CASTILLO CASTAÑEDA RAMON GAXIOLA ROBLES LIA CELINA MENDEZ RODRIGUEZ TANIA ZENTENO SAVIN (2014)

"Introducción: La leche materna es una combinación específica de nutrientes y factores inmunológicos; sin embargo, sus componentes pueden estar expuestos a procesos de oxidación, mismos que pueden ser contrarrestados por moléculas antioxidantes como vitaminas y enzimas, entre otros. Tanto las defensas antioxidantes como el daño oxidativo pueden ser afectados por la edad, número de gestas y otros factores. Objetivo: Comparar el contenido de antioxidantes e indicadores de daño oxidativo en leche materna de acuerdo a la edad de las mujeres y el número de gestas. Metodología: Se midió la actividad de las principales enzimas antioxidantes, la concentración de glutatión, el daño oxidativo a lípidos (sustancias reactivas al ácido tiobarbitúrico, TBARS) y daño a proteínas (carbonilos proteicos) en leche materna utilizando técnicas espectrofotométricas. Se agruparon los datos de acuerdo al número de gestas (1, 2 y 3 o más) y se correlacionó con la edad de las madres. Resultados: Se encontraron diferencias significativas en los niveles de TBARS (p = 0.04) y la actividad de glutatión S-transferasa (GST, p < 0.01) entre los grupos de acuerdo al número de gestas. Así mismo, se encontraron correlaciones lineales entre la edad, el daño oxidativo a lípidos y la actividad de GST. Conclusión: La edad y el número de gestas al parecer incrementan la oxidación de los lípidos presentes en leche materna debido al aumento en el metabolismo y la producción de especies reactivas de oxígeno. Sin embargo, los niveles de TBARS se mantienen relativamente bajos posiblemente debido a las defensas antioxidantes, particularmente GST, de la madre."

"Introduction: Breast milk is a specific combination of nutrients and immunologic factors; however, milk components may be exposed to oxidation processes, which can in turn be counteracted by antioxidant molecules such as vitamins and antioxidant enzymes, amongst others. Both antioxidant defences and oxidative damage can be affected by age, number of pregnancies and other factors. Objective: To compare antioxidant defences and oxidative damage indicators in breast milk, according to age of women and number of pregnancies.

Method: Activity of the main antioxidant enzymes, glutathione concentration, oxidative damage to lipids (thiobarbituric acid reactive substances, TBARS) and oxidative damage to proteins (protein carbonyls) was measured in breast milk using spectrophotometric techniques. Data were grouped according to number of pregnancies (1, 2 and 3 or more) and were related to the age of mothers. Results: Significant differences among groups according to number of pregnancies were found in TBARS levels (p = 0.04) and GST activity (p < 0.01). Also linear correlations between age, lipid peroxidation and GST activity were found. Conclusion: The age and number of pregnancies apparently increase lipid oxidation in milk due to increased metabolism and production of reactive oxygen species.

However, TBARS levels remain relatively low probably because of the mother’s antioxidant defenses, particularly GST."

Article

Leche materna, Edad,Número de gestas, Estrés oxidativo, Enzimas antioxidantes Breast milk, Age, Number of pregnancies, Oxidative stress, Antioxidant enzymes BIOLOGÍA Y QUÍMICA CIENCIAS DE LA VIDA BIOLOGÍA HUMANA ENZIMOLOGIA

Análisis de tendencias en valores extremos de variables meteorológicas importantes para la agricultura

MARIA ESPERANZA BLANCO RAMIREZ (2012)

Tesis (Maestría en Ciencias, especialista en Estadística).- Colegio de Postgraduados, 2012.

Se propone una metodología basada en la teoría de valores extremos para investigar cambios espacio temporales en la tendencia a largo plazo de variables meteorológicas (precipitación y temperatura). Se presenta un ejemplo de aplicación para el estado de Durango, México, analizando los máximos anuales de las variables temperatura máxima, temperatura mínima y precipitación ocurridos durante el período de 1961 a 2000. Esta metodología puede ser de utilidad en la investigación del cambio climático a nivel regional. Los resultados se presentan en mapas de tendencias de eventos extremos. Para el caso del estado de Durango se observan cambios en el comportamiento de eventos extremos, manifestándose una clara tendencia a la ocurrencia de años más secos y más cálidos en algunas zonas del Estado y de la República mexicana, esta metodología se sugiere para tomar decisiones por zonas geográficas. Se detectan tendencias usando el modelo VGLM (Vector Generalized Linear Models), que pertenece a la familia VGAM (Vector Generalized Additive Models). Los mapas de tendencias en los coeficientes de regresión se generan a partir del método de interpolación Kriging simple con el programa ArcGIS 8.1. Las conclusiones son las siguientes: VGLM permite modelar datos de valores extremos, la metodología que se propone, es una alternativa para el caso de datos de valores extremos, puede ser de utilidad en la investigación de cambio climático, los mapas de tendencia pueden usarse, para monitorear los posibles cambios en variables climáticas y anticipar escenarios ante un eventual cambio climático. ANALYSIS OF TRENDS IN EXTREME VALUES OF METEOROLOGICAL VARIABLES RELEVANT TO AGRICULTURE. ABSTRACT: A methodology based on extreme value theory is proposed to investigate spatio-temporal changes in the long-term trend of the meteorological variables precipitation and temperature. We present an application for the state of Durango Mexico, analyzing the variables annual maximum temperature, minimum temperature and precipitation occurred during the time period 1961-2000. This methodology can be useful on studying climate change. The presented results are trend maps of extreme events. For the case of Durango State and Mexican Republic, time changes in the behavior of extreme events are present, showing a clear trend towards the occurrence of dry years and warmer temperatures in some areas of the state, present trend maps for Mexico, suggest this methodology to take decisions geographical areas. Trends are detected using the model VGLM (Vector Generalized Linear Models), which belongs to VGAM (Vector Generalized Additive Models). The maps of trends in the regression coe cients are generated from simple Kriging interpolation method in ArcGIS 8.1. The conclusions are as follows: VGLM allows modeling extreme value data, the proposed methodology is an alternative to the case of extreme value data, can be useful in the investigation of climate change, the trend maps can be used to monitor possible changes in climate variables and settings to anticipate a possible climate change

Master thesis

Series de tiempo Modelo Lineal Vectorial Generalizado Interpolación espacial Time series Extreme value theory Vector generalized linear model Spatial interpolation Estadísica Maestría CIENCIAS SOCIALES

An extension of generalized linear models

EDUARDO GUTIERREZ GONZALEZ ANA LAURA REYES OLVERA (2011)

"In this paper, a general model is proposed to extend generalized linear models to non monotonic link functions. In order to determine the best model, different link function families are analysed, and through AIC, the best model is chosen. Moreover, using asymptotic properties of maximum likelihood estimates are calculated with confidence intervals and hypothesis tests for each of the parameters. Lastly, one example of regression extension is proposed for the bernoulli distribution applied to in vitro germination of leucocoryne coquimbensis seeds."

Article

Generalized linear model Link function AIC Bernoulli distribution CIENCIAS SOCIALES

Oxidative stress in aging: advances in proteomic approaches

DANIEL ORTUÑO SAHAGUN Mercè Pallàs ARGELIA ESPERANZA ROJAS MAYORQUIN (2014)

Abstract: Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL). Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS) and oxidative stress in aging.

Conclusion: One limitation of some of the reports presented here is that details regarding animal ages, care, and behavior assessments/measures are limited, which impedes cross-study comparison and meta-analyses. Also, cell types and their particular characteristics rendered comparison of the effect of ROS on RBC or neurons difficult, for example, as well as under in vitro or in vivo conditions. Thus, therefore more and wider studies are needed.

In humans, it is difficult to compare among proteomic studies because of insufficient characterization of the study material, the small number of patients involved in studies, and variations in experimental designs. At present, basic aging research has arrived at a pharmaceutical phase, with the testing of novel drugs designed to extend a healthy life by targeting specific biochemical pathways, perhaps in specific organs [123]. In this respect, the National Institute on Aging Interventions Testing Program (ITP) experimentally evaluates chemical compounds with potential senescence-retarding effects that can be administered to mice in food or water [124]. While initial results are far from surprising, the experimental design is robust; therefore, it will be useful in order to develop a similar program in mouse genetics in aging.

It is evident that the sole fact of identifying the whole genome sequence of an organism, or to know the whole isoforms and modifications of its products (proteins), is not sufficient for complete elucidation of the aging process. It is necessary to integrate all of this information in a functional manner that reflects more precisely the real situation. Therefore, as important as the generation of all “omic” information is, the development of instruments to analyze and evaluate this efficiently is equally important. In this regard, bioinformatics and computational biology are devoted to performing these analyses, both based on systems biology, that is, the construction of gene, protein, and metabolic pathway networks that interact among them to constitute functional modules (Figure 1). In turn, they integrate design models for prediction from clinical phenotypes to diagnostic and therapeutic strategies after experimentation takes place. Albeit proteomics has already contributed relevant insights in the field of aging research and attempts have been made, in animal models such as mice to map aging-related brain proteins within the context of the biological processes involved [51]; a reference mapping of proteins in healthy aging human subjects has yet to be performed. Nonetheless, with the continued advances in proteomic technology, the study of the proteome during aging is entering a brand new phase of discovery.

Article

BIOLOGÍA Y QUÍMICA Ciencias de la vida Biología celular Fenómenos fisiológicos Crecimiento y desarrollo Envejecimiento (patología) Envejecimiento (metabolismo) Estrés oxidativo Cell biology Physiological phenomena Growth and development Aging (pathology) Aging (metabolism) Oxidative stress

Toxicology of antimicrobial nanoparticles for prosthetic devices

Rosa Elvira Nuñez-Anita Laura Susana Acosta_Torres JUAN CARLOS MARTINEZ ESPINOSA Javier De La Fuente Hernández VICTOR MANUEL CASTAÑO MENESES (2014)

Advances in nanotechnology are producing an accelerated proliferation of new nanomaterial composites that are likely to become an important source of engineered health-related products. Nanoparticles with antifungal effects are of great interest in the formulation of microbicidal materials. Fungi are found as innocuous commensals and colonize various habitats in and on humans, especially the skin and mucosa. As growth on surfaces is a natural part of the Candida spp. lifestyle, one can expect that Candida organisms colonize prosthetic devices, such as dentures. Macromolecular systems, due to their properties, allow efficient use of these materials in various fields, including the creation of reinforced nanoparticle polymers with antimicrobial activity. This review briefly summarizes the results of studies conducted during the past decade and especially in the last few years focused on the toxicity of different antimicrobial polymers and factors influencing their activities, as well as the main applications of antimicrobial polymers in dentistry. The present study addresses aspects that are often overlooked in nanotoxicology studies, such as careful time-dependent characterization of agglomeration and ion release.

The authors thank the following DGPA-UNAM supporting programs: PAPIME-PE202214 and PAPIIT-TA200414. Victor M Castaño is on sabbatical leave at CIATEQ-Queretaro.

Article

Cytotoxicity Oxidative stress Genotoxicity Antifungal effect Denture bases MEDICINA Y CIENCIAS DE LA SALUD CIENCIAS MÉDICAS OTRAS ESPECIALIDADES MÉDICAS

Oxidative stress in aging: advances in proteomic approaches

DANIEL ORTUÑO SAHAGUN Mercè Pallàs ARGELIA ESPERANZA ROJAS MAYORQUIN (2014)

Abstract: Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL). Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS) and oxidative stress in aging.

Conclusion: One limitation of some of the reports presented here is that details regarding animal ages, care, and behavior assessments/measures are limited, which impedes cross-study comparison and meta-analyses. Also, cell types and their particular characteristics rendered comparison of the effect of ROS on RBC or neurons difficult, for example, as well as under in vitro or in vivo conditions. Thus, therefore more and wider studies are needed.

In humans, it is difficult to compare among proteomic studies because of insufficient characterization of the study material, the small number of patients involved in studies, and variations in experimental designs. At present, basic aging research has arrived at a pharmaceutical phase, with the testing of novel drugs designed to extend a healthy life by targeting specific biochemical pathways, perhaps in specific organs [123]. In this respect, the National Institute on Aging Interventions Testing Program (ITP) experimentally evaluates chemical compounds with potential senescence-retarding effects that can be administered to mice in food or water [124]. While initial results are far from surprising, the experimental design is robust; therefore, it will be useful in order to develop a similar program in mouse genetics in aging.

It is evident that the sole fact of identifying the whole genome sequence of an organism, or to know the whole isoforms and modifications of its products (proteins), is not sufficient for complete elucidation of the aging process. It is necessary to integrate all of this information in a functional manner that reflects more precisely the real situation. Therefore, as important as the generation of all “omic” information is, the development of instruments to analyze and evaluate this efficiently is equally important. In this regard, bioinformatics and computational biology are devoted to performing these analyses, both based on systems biology, that is, the construction of gene, protein, and metabolic pathway networks that interact among them to constitute functional modules (Figure 1). In turn, they integrate design models for prediction from clinical phenotypes to diagnostic and therapeutic strategies after experimentation takes place. Albeit proteomics has already contributed relevant insights in the field of aging research and attempts have been made, in animal models such as mice to map aging-related brain proteins within the context of the biological processes involved [51]; a reference mapping of proteins in healthy aging human subjects has yet to be performed. Nonetheless, with the continued advances in proteomic technology, the study of the proteome during aging is entering a brand new phase of discovery.

Article

BIOLOGÍA Y QUÍMICA Ciencias de la vida Biología celular Fenómenos fisiológicos Crecimiento y desarrollo Envejecimiento (patología) Envejecimiento (metabolismo) Estrés oxidativo Cell biology Physiological phenomena Growth and development Aging (pathology) Aging (metabolism) Oxidative stress

Hormesis: lo que no mata, fortalece

NORMA EDITH LOPEZ DIAZ GUERRERO VIRIDIANA YAZMIN GONZALEZ PUERTOS René José Hernández Bautista ADRIANA ALARCON AGUILAR ARMANDO LUNA LOPEZ MINA KONIGSBERG FAINSTEIN (2013)

A lo largo de la evolución, los organismos vivos han tenido que adaptarse a condiciones y agentes adversos para lograr sobrevivir, por lo que han desarrollado diversos y complejos mecanismos para lidiar con ellos. Actualmente, se han identificado una serie de procesos conservados durante los cuales una dosis baja o subletal de un agente o estímulo estresante es capaz de activar una respuesta adaptativa que incrementa la resistencia de una célula u organismo frente a un estrés más severo. A esta respuesta se le conoce como hormesis. Existen una gran cantidad de agentes horméticos entre los que se encuentran la radiación, el calor, los metales pesados, los antibióticos, el etanol, los agentes prooxidantes, el ejercicio y la restricción alimentaria. La respuesta hermética involucra la expresión de una gran cantidad de genes que codifican para proteínas citoprotectoras como las chaperonas del tipo de las que responden a estrés térmico, las enzimas antioxidantes, los factores de crecimiento, las metalotioneínas, entre otros. En esta revisión se explorará la respuesta hormética particularmente frente al estrés oxidante, en especial durante el envejecimiento y la senescencia celular, así como en algunos padecimientos como la diabetes y las enfermedades neurodegenerativas.

Article

BIOLOGÍA Y QUÍMICA Ciencias de la vida Biología celular Hormesis Estrés oxidativo Enfermedades del sistema endócrino Diabetes mellitus Envejecimiento Senescencia Adaptación Cell biology Oxidative stress Endocrine system diseases Aging Senescence Adaptation

Cholesterol overload in the liver aggravates oxidative stress-mediated DNA damage and accelerates hepatocarcinogenesis

GLORIA CRISTINA ENRIQUEZ CORTINA OSCAR BELLO MONROY DIANA PATRICIA ROSALES CRUZ VERONICA SOUZA ARROYO ROXANA URI MIRANDA LABRA RAFAEL TOLEDO PEREZ ARMANDO LUNA LOPEZ ARTURO SIMONI NIEVES Rogelio Hernández-Pando MARIA CONCEPCION GUTIERREZ RUIZ Diego Francesco CALVISI Jens Marquardt LETICIA BUCIO ORTIZ LUIS ENRIQUE GOMEZ QUIROZ (2017)

Primary liver cancers represent the second leading cause of cancer-related deaths worldwide. Diverse etiological factors include chronic viral hepatitis, aflatoxin and alcohol exposure as well as aberrant liver lipid overload. Cholesterol has been identified as a key inducer of metabolic impairment, oxidative stress and promoter of cellular dysfunction. The aim of this work was to address the oxidative stress-mediated DNA damage induced by cholesterol overload, and its role in the development of hepatocellular carcinoma.

C57BL/6 male mice were fed with a high cholesterol diet, followed by a single dose of N-diethylnitrosamine (DEN, 10 μg/g, ip). Reactive oxygen species generation, DNA oxidation, antioxidant and DNA repair proteins were analyzed at different time points. Diet-induced cholesterol overload caused enhanced oxidative DNA damage in the liver and was associated with a decrease in key DNA repair genes as early as 7 days. Interestingly, we found a cell survival response, induced by cholesterol, judged by a decrement in Bax to Bcl2 ratio. Importantly, N-acetyl-cysteine supplementation significantly prevented DNA oxidation damage. Furthermore, at 8 months after DEN administration, tumor growth was significantly enhanced in mice under cholesterol diet in comparison to control animals. Together, these results suggest that cholesterol overload exerts an oxidative stress-mediated effects and promotes the development of liver cancer.

Article

MEDICINA Y CIENCIAS DE LA SALUD BIOLOGÍA Y QUÍMICA Colesterol Estrés oxidativo Daño de ADN Carcinogenesis Hígado Cáncer Cholesterol Oxidative Stress DNA Damage