PUBLICATION
Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure
- Authors
- Liao, S., Yang, W., Yu, T., Dai, L., Liu, X., Zhang, J., Zhao, J., Liu, C.
- ID
- ZDB-PUB-210929-11
- Date
- 2021
- Source
- Biomolecules 11(9): (Journal)
- Registered Authors
- Liu, Chi
- Keywords
- acute renal failure (ARF), cardiorenal syndrome (CRS), drug screening, metronidazole (MTZ), nitroreductase (NTR), zebrafish model
- MeSH Terms
-
- Acute Kidney Injury/complications*
- Acute Kidney Injury/pathology
- Acute Kidney Injury/physiopathology
- Animals
- Animals, Genetically Modified
- Cardio-Renal Syndrome/drug therapy
- Cardio-Renal Syndrome/etiology
- Cardiovascular Diseases/drug therapy*
- Cardiovascular Diseases/etiology*
- Cardiovascular Diseases/pathology
- Digoxin/pharmacology
- Digoxin/therapeutic use
- Disease Models, Animal
- Drug Evaluation, Preclinical*
- Enalapril/pharmacology
- Enalapril/therapeutic use
- Epithelial Cells/pathology
- Humans
- Kidney Tubules/pathology
- Kidney Tubules/physiopathology
- Larva/physiology
- Metronidazole
- Regional Blood Flow/drug effects
- Thioctic Acid/pharmacology
- Thioctic Acid/therapeutic use
- Treatment Outcome
- Zebrafish
- PubMed
- 34572583 Full text @ Biomolecules
Citation
Liao, S., Yang, W., Yu, T., Dai, L., Liu, X., Zhang, J., Zhao, J., Liu, C. (2021) Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure. Biomolecules. 11(9):.
Abstract
Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a Tg(cdh17:Dendra2-NTR) transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping