Mathematical Modeling of Liver Metabolic Activity Under Ex Vivo Conditions upon Exposure to Magnetic Nanoparticles.

Background: In liver transplantation, maintaining donor organ viability is a critical factor determining transplant outcomes. The aim of this study was to evaluate liver metabolic activity under ex vivo perfusion in the presence of magnetite magnetic nanoparticles using mathematical modeling. Methods: Ex vivo liver perfusion was performed with nanoparticles added to the perfusate; the concentration of nanoparticles in the inflowing and outflowing perfusate was determined by mass spectrometry. A stoichiometric model of hepatic metabolic fluxes was constructed, and the distribution of energy resources was assessed using the Zipf-Pareto law and its linear approximation, the Zipf-Pareto-Mandelbrot distribution. Results: It was shown that nanoparticle uptake by the liver increased from 26.5% to 54.4% over the course of perfusion. The introduction of magnetic nanocomposites altered metabolic fluxes, including glycolysis, the respiratory chain, and oxygen exchange across the surface, leading to redistribution of energy resources within liver cells. Zipf-Pareto analysis showed that energy was optimally distributed among all metabolic fluxes both in the control condition and in the presence of nanoparticles. Conclusions: Magnetic nanoparticles alter liver metabolic activity, but the functional state of the organ remains intact.