Cheng Xiaoxia, Chen Xiaowen, Li Dongliang, Jin Xia, He Jiangyan, Yin Zhan
Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China; University of Chinese Academy of Sciences, Beijing, China.
Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China.
Gen Comp Endocrinol. 2015 Apr 1;214:87-94. doi: 10.1016/j.ygcen.2014.05.029. Epub 2014 Jun 4.
The Metronidazole (MTZ), a widely used antibiotic for treating variations of infections, recently is applied in a powerful tool for specifically ablating cells or tissues when combined with E. coli nitroreductase (NTR). Although some undesired biological effects on eukaryote cells have been reported previously, the toxicological mechanism of MTZ has not been uncovered yet. In current study, we found that MTZ can induce proopiomelanocortin a (pomca) expression in zebrafish larvae. The effect of MTZ is in stage-sensitive and dose-dependent manner. A pro-proliferation activity of MTZ on pomca-expressing cells in the pituitary at larval stage was also observed. Furthermore, up-regulated levels of prolactin (prl) and glycoprotein hormone subunit α (gsuα) were also observed after the MTZ treatment. Therefore, utilizing our zebrafish as in vivo model, we concluded that MTZ can interfere the endocrine signals in the pituitary hormone genes expression. Our current results raised the cautions to the intensively application of MTZ in clinical practices and biomedical researches.
甲硝唑（MTZ）是一种广泛用于治疗多种感染的抗生素，最近它与大肠杆菌硝基还原酶（NTR）联合使用时，成为了一种特异性消融细胞或组织的有力工具。尽管此前已有关于其对真核细胞产生一些不良生物学效应的报道，但MTZ的毒理学机制尚未被揭示。在当前的研究中，我们发现MTZ可诱导斑马鱼幼体中阿黑皮素原a（pomca）的表达。MTZ的这种作用具有阶段敏感性和剂量依赖性。我们还观察到MTZ对幼体阶段垂体中表达pomca的细胞具有促增殖活性。此外，MTZ处理后还观察到催乳素（prl）和糖蛋白激素亚基α（gsuα）水平上调。因此，利用我们的斑马鱼作为体内模型，我们得出结论，MTZ可干扰垂体激素基因表达中的内分泌信号。我们目前的研究结果为MTZ在临床实践和生物医学研究中的广泛应用敲响了警钟。
