posted on 2024-02-12, 07:03authored byMerel A. van der Most, Wouter Bakker, Sebastiaan Wesseling, Nico W. van den Brink
The nematode Caenorhabditis elegans is a valuable model for ecotoxicological research, yet limited attention
has been given to understanding how it absorbs, distributes, metabolizes,
and excretes chemicals. This is crucial for C. elegans because the organism is known to have strong uptake barriers that
are known to be susceptible to potential confounding effects of the
presence of Escherichia coli as a food
source. One frequently studied compound in C. elegans is the antidepressant fluoxetine, which has an active metabolite
norfluoxetine. In this study, we evaluated the toxicokinetics and
relative potency of norfluoxetine and fluoxetine in chemotaxis and
activity tests. Toxicokinetics experiments were conducted with varying
times, concentrations of fluoxetine, and in the absence or presence
of E. coli, simulated with a one-compartment
model. Our findings demonstrate that C. elegans can take up fluoxetine and convert it into norfluoxetine. Norfluoxetine
proved slightly more potent and had a longer elimination half-life.
The bioconcentration factor, uptake, and elimination rate constants
depended on exposure levels, duration, and the presence of E. coli in the exposure medium. These findings expand
our understanding of toxicokinetic modeling in C. elegans for different exposure scenarios, underlining the importance of
considering norfluoxetine formation in exposure and bioactivity assessments
of fluoxetine.