Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Affiliated Hospital of Jinggangshan University, Ji'an, 343009, China; Department of Bioscience, College of Life Science, Nanchang University, Nanchang, 330031, China.
Medical of College, Jinggangshan University, Ji'an, 343009, China.
Ecotoxicol Environ Saf. 2020 Sep 15;201:110725. doi: 10.1016/j.ecoenv.2020.110725. Epub 2020 May 29.
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。然而，它会给患者带来许多副作用，其作用机制尚不清楚。在这项研究中，我们将受精后 6 小时（6 hpf）的斑马鱼胚胎暴露于不同浓度的盐酸林可霉素（15、30、60μg/ml）中长达 24 或 96 hpf，以检测其发育毒性和神经毒性，并在受精后 6 天（6 dpf）检测其行为毒性。结果表明，盐酸林可霉素可导致胚胎头部畸形（脑室不清、脑室变小、新生神经元减少）。研究表明，斑马鱼胚胎自发性尾摆动频率在 24 hpf 时增加，暴露于盐酸林可霉素的斑马鱼胚胎在 96 hpf 时心率增加、体长缩短、卵黄囊水肿，并伴有严重的心包水肿。研究还表明，盐酸林可霉素增加了斑马鱼幼鱼的氧化应激水平、乙酰胆碱酯酶（AChE）活性、ATP 酶活性和细胞凋亡。此外，随着盐酸林可霉素浓度的增加，斑马鱼幼鱼的游泳行为减少，但角速度和曲折度增加，这可能是由于 AChE 和 ATP 酶活性降低，以及与神经发育和神经递质系统相关的基因表达减少，导致其运动行为发生变化。总之，我们发现盐酸林可霉素诱导了斑马鱼幼鱼的发育毒性和神经毒性，有助于更全面地评估药物的安全性。
