RESUMEN
The low quality of transplants having undergone hypoxic injury can lead to postoperative complications. The aim of the present research is to estimate, by means of mathematical modeling, how the process of oxygen uptake through the liver surface influences the metabolism of ex vivo perfused liver under hypoxia. The value of oxygen uptake through the surface was established to depend on the degree of oxygenation of the perfusion medium. A decrease in the oxygenation of the perfusion medium resulted in a decreased oxygen uptake through the liver surface. Stoichiometric modeling of the liver metabolism shows that upon the decreased oxygenation of the perfusion medium more energy is required for the process of oxygen uptake through the surface even at a lower level as compared to the normal oxygen supply. The application of the Pareto optimality allows estimating the optimum distribution of the energy resources in liver under ex vivo conditions. Both upon the normal and decreased oxygenation of the perfusion medium, the phenomenon of "free competition" for the resource was observed, with the energy being optimally distributed among all the metabolic fluxes. Moreover, this energy is also spent on the accompanying processes, e.g. for the transport of interstitial fluid.
Asunto(s)
Hipoxia , Consumo de Oxígeno , Humanos , Hipoxia/metabolismo , Hígado/metabolismo , Metabolismo Energético , Oxígeno/metabolismoRESUMEN
We studied the distribution of ferrihydrite nanoparticles isolated from bacteria Klebsiella oxytoca in the whole body in vivo and in a cultured isolated organ (liver). The possibility of controlling these nanoparticles in the body using a magnetic field was assessed. One hour after intravenous injection of ferrihydrite nanoparticles to mice, their accumulation was observed in the liver, lungs, and kidneys. Experiment with cultured isolated rat liver showed that these nanoparticles can be controlled by a magnetic field and the influence of magnetic nanoparticles on the liver over 1 h does not lead to destruction of liver cells associated with the release of the marker enzyme AST. These results show the possibility of using magnetic nanoparticles as a system for controlled drug delivery in the body.
Asunto(s)
Compuestos Férricos/química , Hígado/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Nanopartículas de Magnetita/administración & dosificación , Animales , Animales no Consanguíneos , Compuestos Férricos/farmacocinética , Inyecciones Intravenosas , Riñón/diagnóstico por imagen , Riñón/metabolismo , Klebsiella oxytoca/química , Hígado/metabolismo , Pulmón/metabolismo , Campos Magnéticos , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Masculino , Ratones , Técnicas de Cultivo de Órganos , Ratas , Bazo/diagnóstico por imagen , Bazo/metabolismoRESUMEN
It is shown that the transport of oxygen through the surface of the isolated perfused rat liver is an energy-dependent process that requires the energy of ATP hydrolysis.
Asunto(s)
Adenosina Trifosfato/metabolismo , Hígado/metabolismo , Consumo de Oxígeno , Oxígeno/metabolismo , Animales , Transporte Biológico Activo/efectos de los fármacos , Transporte Biológico Activo/fisiología , Fármacos Cardiovasculares/farmacología , Cobalto/farmacología , Simulación por Computador , Difusión , Técnicas In Vitro , Hígado/efectos de los fármacos , Masculino , Modelos Biológicos , Consumo de Oxígeno/efectos de los fármacos , Ratas WistarRESUMEN
It is convenient to study liver function and metabolism on the model of isolated perfused organ. The results of the present study indicate that viability and metabolic activity of the organ largely depend on the composition of the medium. Under conditions of isolated perfusion, the known pathway of oxygen transport through capillary filtration is supplemented by oxygen delivery to cells through the organ surface making an important contribution to liver oxygenation.