RESUMO
One of the most important causes of disease and premature death in the world is environmental pollution. The presence of pollutants in both water and air contributes to the deterioration of the health of human populations. The Mexico City Metropolitan Area is one of the most populous and affected by air pollution worldwide; in addition, in recent years there has been a growing demand for water, so urban reservoirs such as the Madin dam are vital to meet the demand. However, this reservoir is highly polluted due to the urban settlements around it. Therefore, the aim of the present study was to evaluate oxidative stress in clinically healthy subjects by means of the degree of lipoperoxidation, as well as the modification of serum enzyme levels, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase associated with air and drinking water pollutants from three zones of the Mexico City Metropolitan Area, two of them related to Madin Dam. This descriptive cross-sectional study was conducted between March 2019 and September 2021 in 142 healthy participants (age range 18-65 years). Healthy subjects were confirmed by their medical history. The results showed that chronic exposure to air (SO2) and water pollutants (Al and Fe) was significantly associated with elevated levels of lipoperoxidation. There was evidence that contamination from the Madín dam can generate oxidative stress and affect the health status of people who receive water from this reservoir or who consume fish that inhabit it.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Hepatopatias , Poluentes da Água , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos Transversais , Monitoramento Ambiental , México , Estresse Oxidativo , Projetos Piloto , ÁguaRESUMO
Several studies highlight the presence of aluminum and diclofenac in water bodies around the world and their ability to induce oxidative stress and a negative effect on biomolecules in several aquatic species. However, studies evaluating the toxic effect of mixtures of these contaminants are scarce. The objective of this work was to determine the genotoxic, cytotoxic and embryotoxic effect of the mixture of aluminum and diclofenac at environmentally relevant concentrations on Cyprinus carpio. Juveniles of Cyprinus carpio were exposed to 0.31 µg L-1 of diclofenac, 24.45 mg L-1 of aluminum, and a mixture of both contaminants at the same concentrations for 12, 24, 48, 72 and 96 h. After the exposure time the liver, gills and blood were extracted and the following biomarkers were evaluated: micronucleus frequency, comet assay, caspase activity and TUNEL test. On the other hand, Cyprinus carpio embryos were exposed to diclofenac (0.31 µg L-1), aluminum (0.06 mg L-1) and their mixture at the same concentrations and exposure time. Microscopic observation was performed to evaluate embryonic development at 12, 24, 48, 72 and 96 h. Diclofenac (0.31 µg L-1) induces significant increases in micronucleus frequency with respect to control (p < 0.05), in all tissues. Aluminum (24.45 mg L-1) significantly increases DNA damage index in liver and blood cells with respect to control (p < 0.05). All treatments increase caspases activity in all tissues with respect to control (p < 0.05). Diclofenac increases the percentage of TUNEL-positive cells in liver and blood; while aluminum and the mixture increases it significantly in gills and blood with respect to the control (p < 0.05). The mixture significantly delays embryonic development, while aluminum and the mixture significantly increase teratogenic index with respect to control (p < 0.05). In conclusion, exposure to environmental concentrations of aluminium, diclofenac and their mixture induces genotoxic damage, cell death by apoptosis and negative effects on the development of Cyprinus carpio and the toxic response is modified by the interaction of the xenobiotics.
Assuntos
Alumínio/toxicidade , Carpas , Diclofenaco/toxicidade , Mutagênicos/toxicidade , Teratogênicos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Células Sanguíneas/efeitos dos fármacos , Carpas/embriologia , Carpas/genética , Carpas/metabolismo , Caspase 3/metabolismo , Ensaio Cometa , Dano ao DNA , Interações Medicamentosas , Desenvolvimento Embrionário/efeitos dos fármacos , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes para MicronúcleosRESUMO
The aim of this study was to identify compounds that possess anticonvulsant activity by using a pentylenetetrazol (PTZ)-induced seizure model. Theoretical studies of a set of ligands, explored the binding affinities of the ligands for the GABA(A) receptor (GABA(A)R), including some benzodiazepines. The ligands satisfy the Lipinski rules and contain a pharmacophore core that has been previously reported to be a GABA(A)R activator. To select the ligands with the best physicochemical properties, all of the compounds were analyzed by quantum mechanics and the energies of the highest occupied molecular orbital and lowest unoccupied molecular orbital were determined. Docking calculations between the ligands and the GABA(A)R were used to identify the complexes with the highest Gibbs binding energies. The identified compound D1 (dibenzo(b,f)(1,4)diazocine-6,11(5H,12H)-dione) was synthesized, experimentally tested, and the GABA(A)R-D1 complex was submitted to 12-ns-long molecular dynamics (MD) simulations to corroborate the binding conformation obtained by docking techniques. MD simulations were also used to analyze the decomposition of the Gibbs binding energy of the residues involved in the stabilization of the complex. To validate our theoretical results, molecular docking and MD simulations were also performed for three reference compounds that are currently in commercial use: clonazepam (CLZ), zolpidem and eszopiclone. The theoretical results show that the GABA(A)R-D1, and GABA(A)R-CLZ complexes bind to the benzodiazepine binding site, share a similar map of binding residues, and have similar Gibbs binding energies and entropic components. Experimental studies using a PTZ-induced seizure model showed that D1 possesses similar activity to CLZ, which corroborates the predicted binding free energy identified by theoretical calculations.
Assuntos
Anticonvulsivantes/química , Antagonistas de Receptores de GABA-A/química , Receptores de GABA-A/química , Convulsões/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Sítios de Ligação , Antagonistas de Receptores de GABA-A/uso terapêutico , Humanos , Ligantes , Simulação de Dinâmica Molecular , Conformação Proteica , Receptores de GABA-A/metabolismo , Convulsões/patologiaRESUMO
Este escrito comprende una revisión bibliográfica sobre la obesidad infantil en México desde el año 2000 a 2012. La obesidad constituye un problema de salud pública la cual recientemente ha alcanzado proporciones de epidemia en algunos países. Esta patología constituye el principal problema de malnutrición en el adulto y es una enfermedad que ha aumentado notoriamente en la población infantil, ya que se calcula que más de 40 millones de niños padecen sobrepeso u obesidad. Es un trastorno multifactorial en cuya etiopatogenia están implicados factores genéticos, metabólicos, psicosociales y ambientales, por lo que es difícil distinguir en cada caso en particular la importancia relativa de estos factores. La obesidad infantil es uno de los factores de riesgo vinculados al aumento de enfermedad cardiovascular en el adulto, junto con la hipertensión, hipercolesterolemia y diabetes tipo II; se ha identificado que un factor importante en el desarrollo de la obesidad infantil es la influencia de los medios electrónicos que promueven un estilo de vida básicamente sedentario...
This work is a review of the information about childhood obesity in Mexico from 2000 to 2012. Obesity is a public health problem, which has recently reached epidemic proportions in some countries. This pathology is the main problem of adult malnutrition and has dramatically increased in children, since it is estimated that over 40 million children have overweight or obesity. It involves several factors such as genetic, metabolic, psychosocial and environmental ones. As a result, it is difficult to distinguish their influence in different cases. However, a well-recognized factor in the development of childhood obesity is the media, which promotes a sedentary lifestyle. Childhood obesity is a risk factor associated with cardiovascular disease in adults, hypertension, hypercholesterolemia and diabetes Type II...