PUBLICATION
Ronidazole Is a Superior Prodrug to Metronidazole for Nitroreductase-Mediated Hepatocytes Ablation in Zebrafish Larvae
- Authors
- Chen, Y., Li, P., Chen, T., Liu, H., Wang, P., Dai, X., Zou, Q.
- ID
- ZDB-PUB-230526-36
- Date
- 2023
- Source
- Zebrafish 20(3): 95-102 (Journal)
- Registered Authors
- Zou, Qingliang
- Keywords
- Mtz, NTR, cell ablation, liver regeneration, ronidazole, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Hepatocytes/metabolism
- Humans
- Larva/metabolism
- Metronidazole/toxicity
- Nitroreductases/metabolism
- Prodrugs*/metabolism
- Ronidazole
- Zebrafish*/physiology
- PubMed
- 37229597 Full text @ Zebrafish
Citation
Chen, Y., Li, P., Chen, T., Liu, H., Wang, P., Dai, X., Zou, Q. (2023) Ronidazole Is a Superior Prodrug to Metronidazole for Nitroreductase-Mediated Hepatocytes Ablation in Zebrafish Larvae. Zebrafish. 20(3):95-102.
Abstract
The liver plays a very important role in physiological processes of the human body. Liver regeneration has developed into an important area of study in liver disease. The Mtz (metronidazole)/NTR (nitroreductase)-mediated cell ablation system has been widely used to study the processes and mechanisms of liver injury and regeneration. However, high concentrations and toxic side effects of Mtz severely limit the application of the Mtz/NTR system. Therefore, screening new analogs to replace Mtz has become an important means to optimize the NTR ablation system. In this study, we screened five Mtz analogs including furazolidone, ronidazole, ornidazole, nitromide, and tinidazole. We compared their toxicity on the transgenic fish line Tg(fabp10a: mCherry-NTR) and their specific ablation ability on liver cells. The results showed that Ronidazole at a lower concentration (2 mM) had the same ability to ablate liver cells comparable with that of Mtz (10 mM), almost without toxic side effects on juvenile fish. Further study found that zebrafish hepatocyte injury caused by the Ronidazole/NTR system achieved the same liver regenerative effect as the Mtz/NTR system. The above results show that Ronidazole can replace Mtz with NTR to achieve superior damage and ablation effects in zebrafish liver.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping