The cardiovascular toxicity induced by high doses of gatifloxacin and ciprofloxacin in zebrafish.

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.

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Copyright © 2019. Published by Elsevier Ltd.