Development and Experimental Calibration of the Mathematical Model of Lipid Peroxidation in Mouse Liver Slices.
Interim rept. Dec 94-Sep 95,
MANTECH ENVIRONMENTAL TECHNOLOGY INC DAYTON OH
Pagination or Media Count:
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 VAXVMS 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.
- Computer Programming and Software