A semi-mechanistic integrated toxicokinetic-toxicodynamic (TK/TD) model for arsenic(III) in hepatocytes.

ABSTRACT:

Background

A systems engineering approach is presented for describing the kinetics and dynamics that are elicited upon arsenic exposure of human hepatocytes. The mathematical model proposed here tracks the cellular reaction network of inorganic and organic arsenic compounds present in the hepatocyte and analyzes the production of toxicologically potent by-products and the signaling they induce in hepatocytes.

Methods and results

The present modeling effort integrates for the first time a cellular-level semi-mechanistic toxicokinetic (TK) model of arsenic in human hepatocytes with a cellular-level toxicodynamic (TD) model describing the arsenic-induced reactive oxygen species (ROS) burst, the antioxidant response, and the oxidative DNA damage repair process. The antioxidant r

SUBMITTER: Stamatelos SK 

PROVIDER: S-EPMC4026948 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature