Effects of metronidazole on proopiomelanocortin a gene expression in zebrafish

• Metronidazole (MTZ) enhances the expression of pomca in zebrafish pituitary.
• The effect of MTZ on pomca expression is stage-sensitive and dose-dependent.
• MTZ promotes the proliferation of the pomca expressing cells in the pituitary.
• Up-regulated expressions of prl and gsuα were seen in the MTZ-treated pituitary.

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.