Environmentally relevant concentration of cypermethrin or/and sulfamethoxazole induce neurotoxicity of grass carp: Involvement of blood-brain barrier, oxidative stress and apoptosis

In water environment, the interaction between environmental pollutants is very complex, among which pesticides and antibiotics are dominant. However, most studies only focus on individual toxic effects, rather combined. In this study, the sub-chronic exposure effect of cypermethrin (CMN, 0.65 μg/L), sulfamethoxazole (SMZ, 0.30 μg/L) and their mixture on grass crap (Ctenopharyngodon idellus) was investigated. The brain tight junction, oxidative stress and apoptosis-related indices were determined after 42 days of exposure. In terms of brain function, acetyl cholinesterase (AChE) activity was significantly inhibited by CMN, SMZ and their mixtures during exposure periods. Obvious histological damage from cellular and subcellular levels were also observed, which were further confirmed by a decrease in tight junction protein levels. Malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) contents were significantly increased by individual compounds and mixtures, in which the content of glutathione (GSH) displayed the opposite trend. In mechanism, nuclear factor (erythrocyte derived 2) like 2(Nrf2) pathway was activated, which may trigger cellular protection to cope with CMN and SMZ exposure. However, apoptosis was also detected from the level of mRNA and histochemistry. In general, these two exogenous induced similar biological responses. The neurotoxicity of CMN was strengthened by SMZ with regard to these indices in most cases and vice versa. This study will reveal the potential co-ecological risks of pesticide and antibiotic in the aquatic organism, and provide basic data for their safety and risk assessment.