Estudio del daño hepático producido por estrés pro-inflamatorio en ratas con diferentes edades

Liver plays an unique role as metabolic center that carries out must of xenobiotics and drugs biotransformation and detoxification. Lipopolysaccharide (LPS), which localizes in the gram-negative bacterial external membrane, is a known immunogen that induces inflammatory responses and enhances reacti...

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Detalles Bibliográficos
Autor: PEDRO POSADAS RODRIGUEZ
Tipo de recurso: tesis de maestría
Estado:Versión publicada
Fecha de publicación:2014
País:México
Institución:Universidad Autónoma Metropolitana
Repositorio:Repositorio Institucional de la UAM Iztapalapa
Idioma:español
OAI Identifier:oai:bindani.izt.uam.mx:2r36tx69c
Acceso en línea:https://doi.org/10.24275/uami.2r36tx69c
Access Level:acceso abierto
Palabra clave:info:eu-repo/classification/LEM/Liver -- Diseases
info:eu-repo/classification/LEM/Inflamación
info:eu-repo/classification/LEM/Hígado -- Enfermedades
info:eu-repo/classification/LEM/Biología experimental
info:eu-repo/classification/LEM/Biology, Experimental
info:eu-repo/classification/LEM/Inflammation
info:eu-repo/classification/cti/3
Descripción
Sumario:Liver plays an unique role as metabolic center that carries out must of xenobiotics and drugs biotransformation and detoxification. Lipopolysaccharide (LPS), which localizes in the gram-negative bacterial external membrane, is a known immunogen that induces inflammatory responses and enhances reactive oxygen species (ROS) generation. Host response to LPS includes the expression of a variety of pro-inflammatory cytokines. When this process is exacerbated it turns into local or systemic tissue damage, leading to physiological detriment. However, the liver is able to induce tissue regeneration by activating different transcription factors that regulate proliferation and repair genes expression; nevertheless this repair capacity decreases with age. Therefore, the aim of this work was to study some of the factors that are regulating cellular processes after liver damage depending on age. An hepatic damage model was developed administrating LPS (0.5 mg/kg) a at different time-points 12, 24, 48, 72 and 96 h. Young (4 months of age) and adult (12 months of age) Wistar rats were used. Plasmatic proinflammatory cytokines such as IL-6 y TNF-α were determined, and an increase was observed at 12 h for both ages, but adult animals presented a higher increment. ALT and AST were determined for general liver injury as well as 8- OHdG for oxidative DNA damage, which was higher in the adult rats suggesting that DNA repair mechanism was slower for these animals. One of the proliferation mechanisms after liver injury is the Dll4-Notch4 pathway, so those two proteins were also evaluated; our results showed a higher expression for both of them in young than in adult animals. Since most cell death after LPS treatment is due to apoptosis, Bax and casp-3 were also evaluated along with p53 as a damage reporter of damage DNA. In these regard we found that damage and death response in young animals is quicker and sustained, which was not the case for the adults. However it might be important to continue with this study and determine other repair mechanisms activated by Dll4-Notch4.