Lincomycin hydrochloride is one of the commonly used drugs in clinic. However, it has many side effects on patients, and its mechanism is still poorly understood. In this study, 6 h post-fertilization (6 hpf) zebrafish embryos were exposed to several concentrations of lincomycin hydrochloride (15, 30, 60 μg/mL) for up to 24 or 96 hpf to detect their developmental toxicity and neurotoxicity, and to 6 days post-fertilization (6 dpf) to detect their behavioral toxicity. Our results showed that lincomycin hydrochloride could lead to embryonic head deformities (unclear ventricles, smaller ventricles, fewer new neurons). The studies showed that the frequency of spontaneous tail flick of zebrafish embryo increased at 24 hpf, and the lincomycin hydrochloride exposed zebrafish embryos showed increased heart rate, shorter body length, and yolk sac edema with severe pericardial edema at 96 hpf. The studies also showed that lincomycin hydrochloride increased oxidative stress level, Acetylcholinesterase (AChE) activity, ATPase activity and apoptosis in zebrafish larvae. In addition, the swimming behavior of zebrafish larvae decreased with the increase of lincomycin hydrochloride concentration, but the angular velocity and meandering degree increased, which might be due to the decreased activity of AChE and ATPase, as well as the decreased expression of genes related to neurodevelopment and neurotransmitter system, leading to the change of their motor behaviors. In summary, we found that lincomycin hydrochloride induced developmental toxicity and neurotoxicity in zebrafish larvae, contributing to a more comprehensive evaluation of the safety of the drug.

盐酸林可霉素是临床上常用的药物之一。但是，它对患者有许多副作用，其机理仍知之甚少。在这项研究中，将受精后6 h（6 hpf）的斑马鱼胚胎暴露于数种浓度的盐酸林可霉素（15、30、60μg/ mL）中达24或96 hpf，以检测其发育毒性和神经毒性，并观察受精后6天（6 dpf）以检测其行为毒性。我们的结果表明，盐酸林可霉素可导致胚胎头部畸形（心室不清晰，心室较小，新神经元较少）。研究表明，斑马鱼胚胎自发甩尾的频率在24 hpf时增加，暴露于盐酸林可霉素的斑马鱼胚胎显示出心律加快，体长缩短，96 hpf时卵黄囊水肿伴严重心包水肿。研究还表明，盐酸林可霉素可提高斑马鱼幼虫的氧化应激水平，乙酰胆碱酯酶（AChE）活性，ATPase活性和细胞凋亡。此外，斑马鱼幼虫的游泳行为随盐酸林可霉素浓度的增加而降低，但角速度和曲折度增加，这可能是由于AChE和ATPase活性降低，以及与之相关的基因表达降低所致。神经发育和神经递质系统，导致其运动行为的改变。总之，我们发现盐酸林可霉素在斑马鱼幼虫中诱导了发育毒性和神经毒性，有助于更全面地评估该药物的安全性。