Are\nEnvironmental Levels of Nonsteroidal Anti-Inflammatory\nDrugs a Reason for Concern? Chronic Life-Cycle Effects of Naproxen\nin Zebrafish

The\nnonsteroidal anti-inflammatory drug naproxen (NPX) is among\nthe most consumed pharmaceuticals worldwide, being detected in surface\nwaters within the ng to μg/L range. Considering the limited\nchronic ecotoxicity data available for NPX in aquatic ecosystems,\nthe present study aimed at evaluating its impact in the model organism Danio rerio, following a full life-cycle exposure\nto environmentally relevant concentrations (0.1 to 5.0 μg/L).\nAn integration of apical endpoints, i.e., survival, growth, and reproduction,\nwith gonad histopathology and gene transcription (RNA-seq) was performed\nto provide additional insights into the mode of action (MoA) of NPX.\nNPX decreased zebrafish growth and reproduction and led to histopathological\nalterations in gonads at concentrations as low as 0.1 μg/L.\nAt the molecular level, 0.7 μg/L of NPX led to a disruption\nin gonads transcription of genes involved in several biological processes\nassociated with reproduction, mainly involving steroid hormone biosynthesis\nand epigenetic/epitranscriptomic machineries. Collectively, these\nresults show that environmentally realistic concentrations of NPX\naffect zebrafish reproduction and associated signaling pathways, indicating\nthat current hazard and risk assessment data for NPX underestimate\nthe environmental risk of this pharmaceutical.