Chronic exposure to environmentally relevant concentrations of guanylurea induces neurotoxicity of Danio rerio adults

Recent studies have shown guanylurea (GUA) alters the growth and development of fish, induces oxidative stress, and disrupts the levels and expression of several genes, metabolites, and proteins related to the overall fitness of fish. Nonetheless, up to date, no study has assessed the potential neurotoxic effects that GUA may induce in non-target organisms. To fill the current knowledge gaps about the effects of this metabolite in the central nervous system of fish, we aimed to determine whether or not environmentally relevant concentrations of this metabolite may disrupt the behavior, redox status, AChE activity in Danio rerio adults. In addition, we also meant to assess if 25, 50, and 200 μg/L of GUA can alter the expression of several antioxidant defenses-, apoptosis-, AMPK pathway-, and neuronal communication-related genes in the brain of fish exposed for four months to GUA. Our results demonstrated that chronic exposure to GUA altered the swimming behavior of D. rerio, as fish remained more time frozen and traveled less distance in the tank compared to the control group. Moreover, this metabolite significantly increased the levels of oxidative damage biomarkers and inhibited the activity of acetylcholinesterase of fish in a concentration-dependent manner. Concerning gene expression, environmentally relevant concentrations of GUA downregulated the expression GRID2IP, PCDH17, and PCDH19, but upregulated Nrf1, Nrf2, p53, BAX, CASP3, PRKAA1, PRKAA2, and APP in fish after four months of exposure. Collectively, we can conclude that GUA may alter the homeostasis of several essential brain biomarkers, generating anxiety-like behavior in fish. [Display omitted] •Guanylurea induces an anxiety-like state in fish after four months of exposure.•Chronic exposure to guanylurea promotes the production of ROS in the brain.•Fish exposed to guanylurea showed a significant decrease in acetylcholinesterase activity.•This metabolite upregulated the expression of p53, BAX, CASP3 in the brain.•Guanylurea is likely to produce B-amyloid aggregates in the brain as metformin does.