. Oxidative stress as regulator of neuronal impairment after exposure to hospital effluents in Danio rerio

Abstract

The variety of activities carried out within hospitals results in their "nal discharges being considered hotspots for the emission of emerging pollutants. Hospital ef!uents contain different substances capable of altering the health of eco- systems and biota, furthermore, little research has been done to elucidate the adverse effects of these anthropogenic matrices. Taking this into account, herein we aimed to establish whether exposure to different proportions (2 %, 2.5 %, 3 %, and 3.5 %) of hospital ef!uent treated by hospital wastewater treatment plant (HWWTP) can induce ox- idative stress, behavioral alterations, neurotoxicity, and disruption of gene expression in Danio rerio brain. Our results demonstrate that the hospital ef!uent under-study induces an anxiety-like state and alters swimming behavior, as "sh exhibited increased freezing episodes, erratic movements and traveled less distance than the control group. In addi- tion, after exposure we observed a meaningful rise in biomarkers related to oxidative damage, such as protein carbonyl content (PCC), lipoperoxidation level (LPX), hydroperoxide content (HPC), as well as an increase in enzyme antioxi- dant activities of catalase (CAT), and superoxide dismutase (SOD) upon short-term exposure. Moreover, we discovered an inhibition of acetylcholinesterase (AChE) activity in a hospital ef!uent proportion-dependent manner. Regarding gene expression, a signi"cant disruption of genes related to antioxidant response (cat, sod, nrf2), apoptosis (casp6, bax, casp9), and detoxi"cation (cyp1a1) was observed. In conclusion, our outcomes suggest that hospital ef!uents en- hance the emergence of oxidative molecules, and promote a highly oxidative environment at the neuronal level that favors the inhibition of AChE activity, which consequently explains the anxiety-like behavior observed in D. rerio adults. Lastly, our research sheds light on possible toxicodynamic mechanism by which these anthropogenic matrices may trigger damage in D. rerio brain.