Physiologically-based modelling in mice suggests an aggravated loss of clearance capacity after toxic liver damage.

ABSTRACT: Diseases and toxins may lead to death of active liver tissue, resulting in a loss of total clearance capacity at the whole-body level. However, it remains difficult to study, whether the loss of metabolizing tissue is sufficient to explain loss of metabolic capacity of the liver or whether the surviving tissue undergoes an adaptive response to compensate the loss. To understand the cellular impact of toxic liver damage in an in vivo situation, we here used physiologically-based pharmacokinetic modelling to investigate pharmacokinetics of a specifically designed drug cocktail at three different sampling sites of the body in healthy mice and mice treated with carbon tetrachloride (CCl₄). Liver zonation was explicitly quantified in the models through immunostaining of cytochrome P4

SUBMITTER: Schenk A 

PROVIDER: S-EPMC5524914 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature