Development and Experimental Calibration of the Mathematical Model of Lipid Peroxidation in Mouse Liver Slices

摘要

A computerized biologically based pharmacodynamic (BBPD) model was developed in order to describe and simulate chemically induced lipid peroxidation in precision cut mouse liver slices. The model was written in Advanced Continuous Simulation Language (ACSL) and simulations were performed using SIMUSOLY software with optimization capabilities on a VAX/VMS mainframe computer. The BBPD model simulated formation of lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS) over time as a function of the amounts of cytochrome P45O (CYP)-activated chemical inducer and active antioxidants. The rate of peroxidation was controlled by lipid peroxidizability, destruction of CYP, autooxidation, and activity of glutathione peroxidase. The BBPD model was initially parametrized with the literature data for TBARS formation during lipid peroxidation, reported for rat liver slices induced with bromotrichloromethane and tert-butyl hydroperoxide (TBOOH). Then, the biochemical parameters were adjusted to reflect the physiology of the mouse liver, and the BBPD model was used to simulate TBARS formation during lipid peroxidation in precision cut mouse liver slices induce with TBOOH. The BBPD model predictions were in agreement with the experimental data.