TY  - JOUR
A1  - Gehre, Christian
A1  - Flechner, Marie
A1  - Kammerer, Sarah
A1  - Küpper, Jan-Heiner
A1  - Coleman, Charles Dominic
A1  - Püschel, Gerhard Paul
A1  - Uhlig, Katja
A1  - Duschl, Claus
T1  - Real time monitoring of oxygen uptake of hepatocytes in a microreactor using optical microsensors
T2  - Scientific reports
N2  - Most in vitro test systems for the assessment of toxicity are based on endpoint measurements and cannot contribute much to the establishment of mechanistic models, which are crucially important for further progress in this field. Hence, in recent years, much effort has been put into the development of methods that generate kinetic data. Real time measurements of the metabolic activity of cells based on the use of oxygen sensitive microsensor beads have been shown to provide access to the mode of action of compounds in hepatocytes. However, for fully exploiting this approach a detailed knowledge of the microenvironment of the cells is required. In this work, we investigate the cellular behaviour of three types of hepatocytes, HepG2 cells, HepG2-3A4 cells and primary mouse hepatocytes, towards their exposure to acetaminophen when the availability of oxygen for the cell is systematically varied. We show that the relative emergence of two modes of action, one NAPQI dependent and the other one transient and NAPQI independent, scale with expression level of CYP3A4. The transient cellular response associated to mitochondrial respiration is used to characterise the influence of the initial oxygen concentration in the wells before exposure to acetaminophen on the cell behaviour. A simple model is presented to describe the behaviour of the cells in this scenario. It demonstrates the level of control over the role of oxygen supply in these experiments. This is crucial for establishing this approach into a reliable and powerful method for the assessment of toxicity.
Y1  - 2020
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/59869
SN  - 2045-2322
VL  - 10
IS  - 1
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -