摘要
目的本文研究吡嗪酰胺(PZA)对斑马鱼胚胎的发育毒性及其产生机制。方法采用受精后4h的斑马鱼胚胎进行吡嗪酰胺不同浓度的暴露,分别于暴露后24、48、72和96h进行死亡率、孵化率的统计。给药96h后进行斑马鱼幼鱼形态评分、行为学分析、活性氧簇(ROS)和氧化应激指标检测。结果表明吡嗪酰胺显著抑制斑马鱼胚胎孵化,导致斑马鱼幼鱼发育畸形(如卵黄囊吸收迟滞、鱼鳔缺失、心包水肿和体节模糊等),同时吡嗪酰胺的暴露造成斑马鱼幼鱼运动行为能力的降低。吡嗪酰胺的暴露能够引起斑马鱼体内ROS、总超氧化物歧化酶(T-SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)和丙二醛(MDA)水平的变化。结论吡嗪酰胺对斑马鱼胚胎有明显的发育毒性,并呈剂量和时间依赖性,氧化应激在吡嗪酰胺发育毒性中起着重要的作用。
Objective Developmental toxicity and mechanisms of pyrazinamide （PZA） were studied in the present study. Methods The developmental toxicity and oxidative damage of PZA on zebrafish were investigated. The mortality and the hatching rate were recorded at 24, 48, 72 and 96 hours post exposure （hpe）. Additionally, we tested the development score, behavior analysis, the generation of reactive oxygen species （ROS）, the activities of stress-related oxidative enzymes （CAT and SOD） and the content of GSH and MDA. Results The results indicated that PZA severely inhibited the hatching rate at 48 hpe, and resulted in larval malformation at 96 hpe such as yolk sac hysteresis, swim bladder defect, pericardial edema, and shorter body length and so on. Meanwhile, PZA could significantly decrease the locomotive ability of zebrafish. The levels of ROS, SOD, MDA, GSH and CAT were affected at varied degrees, indicating that PZA caused oxidative stress in zebrafish embryos. MDA and CAT levels were significantly higher, whereas GSH level was significantly lower in the PZA treated groups. Conclusion PZA caused developmental toxicity on zebrafish embryos at the early stage in dose- and time-dependent, and oxidative damage played a vital role in the developmental toxicity induced by PZA.
作者
李娟娟
韩利文
邱昌辉
刘可春
孙桂金
何秋霞
田青平
张云
Li Juan-juan;Han Li-wen;Qiu Chang-hui;Liu Ke-chun;Sun Gui-jin;He Qiu-xia;Tian Qing-ping;Zhang Yun(Shanxi Medical University,Taiyuan 030000;Biology Institute,Qilu University of Technology（Shandong Academy of Sciences）,Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences,Shandong Provincial Engineering Laboratory for Biological Testing Technology,Ji＇nan 250103)
出处
《中国抗生素杂志》
CAS
CSCD
2018年第11期1419-1425,共7页
Chinese Journal of Antibiotics
基金
国家自然科学基金(No.81703624)
山东省自然科学基金三院联合基金(No.ZR2015YL010)
关键词
吡嗪酰胺
斑马鱼胚胎
发育毒性
氧化应激
Pyrazinamide（PZA）
Zebrafish embryos
Developmental toxicity
Oxidative stress
