Sertraline Hydrochloride Exposure Leads to Reactive Oxygen Species Burst in Model Microalgae Species (Raphidocelis subcapitata)

Microalgae play important ecological roles and serve
as useful
models for assessing the impacts of environmental contaminants on
lower trophic aquatic organisms. Sertraline, a commonly prescribed
selective serotonin reuptake inhibitor (SSRI) found in urban waters,
has been observed to induce chlorosis in Raphidocelis
subcapitata close to environmentally relevant concentrations.
This study estimated potentially hazardous concentrations of sertraline
hydrochloride by deriving transcriptomic and metabolomic points of
departure (tPODs and mPODs) below which chronic adverse effects would
not be expected. Additionally, an Adverse Outcome Pathway describing
the mechanism by which sertraline hydrochloride impacted R. subcapitata was proposed using a multiomics approach.
The mPOD derived from nontargeted metabolomics was comparable to the
tPOD (455 vs 690 μg/L), and annotated dysregulated metabolites
along with reduced photosynthetic capability indicated that uncoupling
of the cyclic electron flow required for photosynthesis led to a reactive
oxygen species (ROS) burst. This probable ROS burst altered cell membrane
composition and downregulated genes associated with protoporphyrinogen
IX and heme biosynthesis pathways. This research highlights the molecular
mechanisms underlying pharmaceutical-induced chlorosis in a model
microalgae species and demonstrates the utility of integrating metabolomics
and transcriptomics for assessing the potential ecological risks of
SSRIs.