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Koumine is one of the most abundant alkaloids found in Gelsemium elegans , and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medicinal development and use of koumine. We investigated the toxic effects of koumine on the developmental toxicity and behavioral neurotoxicity of zebrafish embryos and larvae. Embryos at 6 h postfertilization (hpf) were exposed to 12.5, 25, 50, 75, and 100 mg/L of koumine until 120 hpf. Koumine affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas. To identify the neurotoxicity of koumine, the behavior of the larvae was measured. Koumine at 50 and 100 mg/L affect the escape response. The embryos exhibited uncoordinated muscle contractions along the body axis in response to touch at 36 hpf. More importantly, we found that the neurotoxicity of koumine is mainly caused by influencing the ACh content and the activity of AChE without impairing motor neuron development. A comprehensive analysis shows that a high concentration of koumine has obvious toxic effects on zebrafish, and the safe concentration of koumine for zebrafish should be less than 25 mg/L. These results will be valuable for better understanding the toxicity of koumine and provide new insights into the application of koumine.

In this study, zebrafish larvae are introduced as an in vivo platform to examine the neurotoxicity and developmental toxicity associated with continuous exposure to a concentration gradient of different sizes of SiO2 nanoparticles (15 nm and 50 nm diameter) to determine the dose effect and size effect of SiO2 nanoparticle (NP)-induced toxicity. Bovine serum albumin (BSA-V) is utilized as a stabilizing agent to prevent coagulation of the SiO2 nanoparticles. To the best of our knowledge, this study is the first to describe locomotor activity assays linking rest/wake behavioral profiles for the purpose of investigating the neurotoxicity of NPs. In addition, developmental toxicological endpoints including mortality, LC50 , malformation, and cartilaginous deformity are assessed. The results show a concentration-dependent increase in behavioral neurotoxicity, mortality, and malformation among larvae treated with the SiO2 nanoparticles of 15 nm and 50 nm. A comparison of the 15 nm and 50 nm NPs by K-means clustering analysis demonstrates that the 15 nm NPs have a greater neurotoxic effect than the 50 nm NPs, with the 50 nm NPs exhibiting greater developmental toxicity on the zebrafish larvae than the 15 nm NPs., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)