Apodemus sylvaticus como centinela de fuentes de contaminación complejas

[spa] La entrada en el medioambiente de xenobióticos, procedentes de la actividad humana, que son biológicamente activos y de difícil eliminación, representa un grado de estrés que, a menudo, resulta inaceptable por los organismos y que con, demasiada frecuencia, se eleva a nivel del ecosistema. Es, por tanto, necesario realizar una vigilancia activa de las fuentes de contaminación conocidas para detectar, de la manera más rápida y fiable posible, las señales de alarma que envían los ecosistemas. Los animales denominados centinelas, a su vez, por su capacidad de integrar la información del hábitat, tanto en el espacio como en el tiempo, pueden actuar como señales de alarma ecológica temprana. Por otro lado, para evaluar el impacto de los peligros por sustancias químicas en los ecosistemas, se han establecido modelos regulatorios que permiten predecir el grado a la que los organismos estarán expuestos, para finalmente evaluar el riesgo. Este abordaje estandarizado, a menudo, ha construido sus algoritmos en base a los valores límites establecidos en ensayos, en condiciones controladas, con modelos de experimentación conocidos. Sin embargo, dada la dotación enzimática, la fisiología o la flora intestinal específica de cada especie y las propiedades toxicocinéticas de los compuestos químicos expuestos, las respuestas pueden variar, por lo que, la extrapolación de los efectos tóxicos de unos organismos a otros debe ser conocida. Para ello, se ha propuesto, por un lado, al ratón de campo, Apodemus sylvaticus, como centinela de contaminación ambiental de tipo crónica, difusa y compleja, por su ubicuidad, su prospección del hábitat y su tolerancia a los contaminantes. Con este objetivo se caracterizó, mediante biomarcadores de exposición y de efecto, al ratón de campo en tres depósitos controlados de residuos de diferentes orígenes y en zonas agrícolas donde se habían vertido lodos de depuradora como fuente de nutrientes. Por otro lado, se utilizó a Apodemus sylvaticus como modelo de experimentación en mesocosmos, a fin de comprender y comparar la respuesta a la exposición de xenobióticos conocidos, con el fin de integrar y mejorar la capacidad predictiva de los modelos. Los resultados han permitido confirmar que el ratón de campo, Apodemus sylvaticus, es capaz de integrar información de la contaminación ambiental mediante el estudio de biomarcadores exposición y de efecto, ya que la exposición a fuentes de contaminación de diversos orígenes produjo una respuesta cuantitativa y diferencial entre las diversas zonas de estudio. De igual manera, Apodemus sylvaticus, ha aportado información relevante sobre los tipos de efectos observados tras la exposición a un tóxico polar o a un toxico de carácter lipofílico, en estudios en mesocosmos, al ser comparado con Mus musculus domesticus, como modelo experimental conocido. Por tanto, podemos concluir que el ratón de campo, Apodemus sylvaticus, es un modelo fiable como centinela de contaminación ambiental, capaz de integrar de manera cuantificable la exposición a xenobióticos.[eng] The release of xenobiotics into the environment, derived from human activity, which are biologically active and difficult to eliminate, represents a degree of stress that is, often, unacceptable to organisms and which, too often, rises to the level of ecosystem. It is, therefore, necessary to carry out an active surveillance of known sources of contamination in order to detect, as fastest and most reliable as possible, the alarm signals sent by the ecosystems. Animals called sentinels because of their ability to integrate habitat information, both in space and time, can act as early ecological warning signals. On the other hand, to assess the impact of the chemical hazards on ecosystems, regulatory models have been established that allow predicting the degree to which organisms will be exposed, to finally assess the risk. However, the responses may vary between species. To this end, it has been proposed, the wood mouse, Apodemus sylvaticus, as a sentinel of chronic, diffuse and complex environmental pollution. With this objective, the wood mouse was characterized, through biomarkers of exposure and effect, in three controlled landfills from different origins and in agricultural areas where sewage sludge had been discharged as a source of nutrients. On the other hand, Apodemus sylvaticus was used as experimental model in mesocosms, in order to understand and compare the response to the exposure of known xenobiotics. The results have confirmed that the wood mouse, Apodemus sylvaticus, is capable of integrating information of the environmental contamination through the study of exposure and effect biomarkers, since the exposure to contamination of different origins produced a quantitative and differential response between the different areas of study. Similarly, Apodemus sylvaticus, has provided relevant information on the types of effects observed, after the exposure to a polar toxic or a lipophilic toxic, in the study in mesocosmos, when it is compared against Mus musculus domesticus, as a known experimental model. Therefore, we can conclude that the wood mouse, Apodemus sylvaticus, is a reliable model as sentinel of environmental contamination, capable of quantitatively integrating exposure to xenobiotics

Los métodos alternativos en el estudio de la seguridad de cosméticos

El Reglamento 1223/2009 establece las normas que deben cumplir todos los productos cosméticos comercializados en Europa, con objeto de velar por el funcionamiento del mercado interior y lograr un elevado nivel de protección de la salud humana garantizando el uso de métodos alternativos que no impliquen la utilización de animales. El Laboratorio Europeo de Referencia para las Alternativas a la Experimentación con Animales (EURL-EURL- ECVAM) es el laboratorio de referencia en Europa encargado de validar los métodos alternativos. Posteriormente pueden ser homologados por la Organización de Cooperación y Desarrollo Económico (OCDE). Por otro lado, el Comité Científico de Seguridad de los Consumidores (SCCS) asesora a la Comisión sobre todos los temas relacionados con la seguridad de los cosméticos. En esta revisión se detalla una relación de métodos alternativos necesarios para evaluar la seguridad de los ingredientes cosméticos así como los métodos usados y sus limitaciones

Lysine-based surfactants in nanovesicle formulations: the role of cationic charge position and hydrophobicity in in vitro cytotoxicity and intracellular delivery

Understanding nanomaterial interactions within cells is of increasing importance for assessing their toxicity and cellular transport. Here, we developed nanovesicles containing bioactive cationic lysine-based amphiphiles, and assessed whether these cationic compounds increase the likelihood of intracellular delivery and modulate toxicity. We found different cytotoxic responses among the formulations, depending on surfactant, cell line and endpoint assayed. The induction of mitochondrial dysfunction, oxidative stress and apoptosis were the general mechanisms underlying cytotoxicity. Fluorescence microscopy analysis demonstrated that nanovesicles were internalized by HeLa cells, and evidenced that their ability to release endocytosed materials into cell cytoplasm depends on the structural parameters of amphiphiles. The cationic charge position and hydrophobicity of surfactants determine the nanovesicle interactions within the cell and, thus, the resulting toxicity and intracellular behavior after cell uptake of the nanomaterial. The insights into some toxicity mechanisms of these new nanomaterials contribute to reducing the uncertainty surrounding their potential health hazards

Gemini pyridinium amphiphiles for the synthesis and stabilization of gold nanoparticles for drug delivery

Hypothesis Gemini pyridinium-based amphiphiles can play a triple role as: gold nanoparticles (AuNPs) synthesis facilitator, particle stabilizer and anion recognition centre. The so formed nanoparticles should be able to bind and release anionic drugs. Experiments We describe (a) Synthesis, by a phase transfer method, of both new organic media and water soluble AuNPs using gemini-type surfactants based on bis-pyridinium salts as ligands, acting as transfer agents into organic media and also as nanoparticle stabilizers, (b) Examination of their stability in solution, (c) Chemical and physical characterization of the nanoparticles, (d) Toxicity data concerning both the bis-pyridinium ligands and the bis-pyridinium coated nanoparticles, and (e) Study of their ability for delivering anionic pharmaceuticals such as ibuprofen and piroxicam. Findings Pyridinium gemini-type surfactants show the ability to play multiple roles such as transfer agent and stabilizer, as well as ionophores: They are responsible for the preparation, stability, and delivery properties of these AuNPs, which gold core is stabilized by the anions present in the bis-pyridinium salts. The tetrahydropyridine resulting from the reduction of the bis-pyridinium salt is capable of reduce gold, due to its spontaneous oxidation to the corresponding pyridinium salt, leading to the formation of stable AuNPs

From Waste to Healing Biopolymers: Biomedical Applications of Bio-Collagenic Materials Extracted from Industrial Leather Residues in Wound Healing

The biomedical properties of a porous bio-collagenic polymer extracted from leather industrial waste residues have been investigated in wound healing and tissue regeneration in induced wounds in rats. Application of the pure undiluted bio-collagen to induced wounds in rats dramatically improved its healing after 7 days in terms of collagen production and wound filling as well as in the migration and differentiation of keratinocytes. The formulation tested was found to be three times more effective than the commercial reference product Catrix® (Heal Progress (HP): 8 ± 1.55 vs. 2.33 ± 0.52, p vs. 2.17 ± 0.75, p vs. 5 ± 5.48, p < 0.05).Rafael Luque gratefully acknowledges support from the Spanish MICINN via the concession of a Ramon y Cajal contract (ref. RYC-2009-04199) and funding under project P10-FQM-6711 (Consejeria de Ciencia e Innovacion, Junta de Andalucia).We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Biomarkers responses and polybrominated diphenyl ethers and their methoxylated analogs measured in Sparus aurata from the Lagoon of Bizerte, Tunisia

This study aimed to the examination of the levels and effects of organobromine compounds (polybrominated diphenyl ethers: PBDEs and methoxylated brominated diphenyl ethers: MeO-PBDEs), in Sparus aurata native to the Lagoon of Bizerte. For that, different biomarkers of exposure (somatic indices, superoxide dismutase, and catalase activities) and effect (malondialdehyde level, histopathologic alterations, and DNA damage) as well as pollutant levels were measured in specimens collected from this impacted ecosystem and the Mediterranean Sea as a reference site. Bizerte Lagoon PBDE fish levels were higher than the Mediterranean Sea, whereas MeO-PBDEs were higher in the reference site. Fish from Bizerte Lagoon presented a higher hepatosomatic index, lower catalase and superoxide dismutase activity, higher level of malondialdehyde, and higher percentage of DNA tail in comparison to fish from the reference area. The histological study of the liver indicated substantial lesions in fish from the polluted site. The results showed strong positive correlations between the concentrations of the PBDE or MeO-PBDE and the MDA and DNA tail % levels and negative correlations for the activities of enzymes of SOD and CAT. Consequently, these findings could suggest a potential link between exposure to these pollutants and the observed biomarker responses in the Bizerte Lagoon seabream. Taken together, these results highlight the importance of biomarker selection and the selected sentinel fish species as useful tools for biomonitoring of aquatic pollution.The Spanish Ministry of Science and Innovation (CEMAGUA-CGL2007-64551/HID) and the Tunisian Ministry of Higher Education and Scientifc Research supported this study. The authors are thankful to R. Chaler, D. Fangul, and M. Comesaña for their help at the mass spectrometry work. We gratefully acknowledge the technical assistance of Joan Serret, David Ramos-López, Javier Gonzalez-Linares, Lydia Camps, Natàlia Brull Barco, and Constança Porredon Guarch in biomarker analysis. The authors would like to express their gratitude to the Deanship of Scientific Research, Saudi Electronic University, Riyadh, Kingdom of Saudi Arabia.Peer reviewe

Lysine-based surfactants in nanovesicle formulations: the role of cationic charge position and hydrophobicity in in vitro cytotoxicity and intracellular delivery

Understanding nanomaterial interactions within cells is of increasing importance for assessing their toxicity and cellular transport. Here, we developed nanovesicles containing bioactive cationic lysine-based amphiphiles, and assessed whether these cationic compounds increase the likelihood of intracellular delivery and modulate toxicity. We found different cytotoxic responses among the formulations, depending on surfactant, cell line and endpoint assayed. The induction of mitochondrial dysfunction, oxidative stress and apoptosis were the general mechanisms underlying cytotoxicity. Fluorescence microscopy analysis demonstrated that nanovesicles were internalized by HeLa cells, and evidenced that their ability to release endocytosed materials into cell cytoplasm depends on the structural parameters of amphiphiles. The cationic charge position and hydrophobicity of surfactants determine the nanovesicle interactions within the cell and, thus, the resulting toxicity and intracellular behavior after cell uptake of the nanomaterial. The insights into some toxicity mechanisms of these new nanomaterials contribute to reducing the uncertainty surrounding their potential health hazards

pi-Donor/pi-Acceptor Interactions for the Encapsulation of Neurotransmitters on Functionalized Polysilicon-Based Microparticles

Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1·4PF6-4·4PF6), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of π-donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1·4PF6, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2). View Full