Ecological Risk Assessment of Environmentally Relevant Concentrations of Propofol on Zebrafish (danio Rerio) at Early Life Stage: Insight into Physiological, Biochemical, and Molecular Aspects

Propofol is an intravenous anesthetic injection extensively used in clinic, which has been proved to be neurotoxic in humans. Improper use and disposal of propofol may lead to its release into the aquatic environment, but the potential ecological risk of propofol to aquatic organisms remains poorly understood. For this study, we comprehensively explored the ecotoxicological effects and potential mechanisms of propofol (0.04, 0.2 and 2 mg L-1) on 120 hpf zebrafish (Danio rerio) embryos from physiological, biochemical, and molecular perspectives. The results showed that propofol has moderate toxicity on zebrafish embryos (96 h LC50 = 4.260 mg L-1), which could significantly reduce the hatchability and delay the development. Propofol can trigger reactive oxygen species (ROS) generation, lipid peroxidation (Malondialdehyde, MDA) and DNA damage (8-hydroxy-2-deoxy-guanosine, 8-OHdG). The glutathione peroxidase (GPX) activity of zebrafish embryos in 0.04 and 0.2 mg L-1 propofol treatment group was activated in response to oxidative damage, while activities of superoxide dis-mutase (SOD), catalase (CAT) and GPX in zebrafish treated with 2 mg L-1 was significant inhibited compared with the control group (p<0.05). Moreover, the expression of antioxidant genes and related pathways was inhibited. Apoptosis was investigated at genes level and histochemistry. Molecular docking confirmed that propofol could change in the secondary structure of acetylcholinesterase (AChE) and competitively inhibited acetylcholine (ACh) binding to AChE, which may disturb the nervous system. These results described toxic response and molecular mechanism in zebrafish embryos, providing multiple aspects about ecological risk assessment of propofol in water environment.