Assessment of Neurotoxicity Following Single and Co-exposure of Cadmium and Mercury in Adult Zebrafish: Behavior Alterations, Oxidative Stress, Gene Expression, and Histological Impairment in Brain

In this study, alterations in behavior, oxidative stress, and related gene expressions, as well as histopathological changes in the brain, of zebrafish were evaluated following exposure to cadmium chloride and mercury chloride alone and in combination for 21 days. In the light–dark preference test, the time spent in the dark side and numbers of entries in the light side by zebrafish of all toxicity groups compared to those of control were significantly higher and lower, respectively. In novel tank test, times spent in the lower zone by zebrafish of toxicity groups were at par but significantly higher compared to those of the control group, which indicate the development of anxiety-like behavior in all toxicity groups. Zebrafish exposed to Cd + Hg showed significant downregulation of Nrf2 mRNA expression (Nrf2— protein that is responsible for the expression of antioxidant proteins) in the brain compared to other toxicity groups. The downregulation of Nrf2 plays a crucial role in cellular oxidative damage in the brain of zebrafish. The glutathione level of the brain was significantly decreased in Cd and Cd + Hg-exposed fish. However, the malondialdehyde level of the brain was significantly higher in Hg and Cd + Hg groups. Significant microscopic pathological changes were noticed in the olfactory bulb, corpus cerebelli, and optic tectum of zebrafish of all toxicity groups. The Cd + Hg-exposed group showed severe changes in periventricular gray zone of optic tectum. Significant synergistic toxicity in the brain was not observed following simultaneous exposure of Cd and Hg in zebrafish. Graphical abstract