College of Bioengineering, Chongqing University, Chongqing 400044, PR China; College of Bioengineering, Beijing Polytechnic, Beijing 100176, PR China.
Research Center of Environmental Engineering Technology, Chongqing Academy of Environmental Science, Chongqing 401120, PR China.
Environ Pollut. 2019 Nov;254(Pt B):112861. doi: 10.1016/j.envpol.2019.07.029. Epub 2019 Jul 9.
As a new type of pollutant, fluoroquinolones (FQs) antibiotics are ubiquitous in environment and have some threat to human health and ecological environment. Their ecological toxicity to the environment urgently need to be assessed. Therefore, we firstly explored the toxic effects and possible mechanism of cardiovascular toxicity induced by gatifloxacin (GTFX) and ciprofloxacin (CPFX) using zebrafish model. After 24 h exposure, the zebrafish treated with GTFX showed pericardial edema which was further investigated by histopathological examination, while CPFX exposure did not induce morphological abnormalities. However, both of them induced cardiac dysfunction, such as decreased heart rate and cardiac output which was showed a positive correlation with the concentration. To better understand the possible molecular mechanisms underlying cardiovascular toxicity in zebrafish, we investigated the transcriptional level of genes related to calcium signaling pathway and cardiac muscle contraction. The results indicated that the expression of ATPase (atp2a1l) and cardiac troponin C (tnnc1a) genes were significantly inhibited, the expression of calcium channel (cacna1ab) gene showed slight promoted trend after CPFX exposure. For zebrafish treated with GTFX, the expression of atp2a1l genes was also significantly inhibited, while the expression of tnnc1a genes was slightly inhibited and cacna1ab genes expression had no obvious effect. The present study firstly revealed that GTFX exposure can induce morphological and functional abnormalities on the cardiovascular system of zebrafish. Though CPFX exposure did not induce morphological abnormalities, the function of cardiovascular system was still damaged. Mechanistically, this toxicity might result from the pressure of down-regulation of genes associated with calcium signaling pathway and cardiac muscle contraction. The results of this study can provide a valuable theoretical basis for the establishment of FQs environmental quality standards in water environment, environmental drug regulation and risk management.
作为一种新型污染物,氟喹诺酮类(FQs)抗生素在环境中普遍存在,对人类健康和生态环境存在一定威胁。其对环境的生态毒性亟待评估。因此,我们首次采用斑马鱼模型探讨了加替沙星(GTFX)和环丙沙星(CPFX)诱导的心血管毒性的毒作用及其可能机制。经 24 h 染毒后,GTFX 处理的斑马鱼出现心包水肿,组织病理学检查进一步证实了这一结果,而 CPFX 暴露并未诱导形态异常。然而,两者均诱导了心脏功能障碍,如心率和心输出量降低,且与浓度呈正相关。为了更好地了解斑马鱼心血管毒性的可能分子机制,我们检测了与钙信号通路和心肌收缩相关基因的转录水平。结果表明,CPFX 暴露后,ATP 酶(atp2a1l)和肌钙蛋白 C(tnnc1a)基因的表达明显受到抑制,钙通道(cacna1ab)基因的表达略有上调。而 GTFX 处理的斑马鱼中,atp2a1l 基因的表达也明显受到抑制,tnnc1a 基因的表达略有抑制,cacna1ab 基因的表达则无明显影响。本研究首次揭示了 GTFX 暴露可引起斑马鱼心血管系统形态和功能异常,而 CPFX 暴露虽未引起形态异常,但仍对心血管系统功能造成损害。其毒性可能与钙信号通路和心肌收缩相关基因下调有关。本研究结果可为水环境中氟喹诺酮类抗生素环境质量标准的制定、环境药物监管和风险管理提供有价值的理论依据。