PUBLICATION
BML-257, a Small Molecule that Protects against Drug-Induced Liver Injury in Zebrafish
- Authors
- Jagtap, U., Basu, S., Lokhande, L., Bharti, N., Sachidanandan, C.
- ID
- ZDB-PUB-220708-9
- Date
- 2022
- Source
- Chemical Research in Toxicology 35(8): 1393-1399 (Journal)
- Registered Authors
- Sachidanandan, Chetana
- Keywords
- none
- MeSH Terms
-
- Chemical and Drug Induced Liver Injury*/metabolism
- Chemical and Drug Induced Liver Injury*/prevention & control
- Hepatocytes
- Acetaminophen/metabolism
- Liver/metabolism
- Animals
- Zebrafish*
- PubMed
- 35796757 Full text @ Chem. Res. Toxicol.
Citation
Jagtap, U., Basu, S., Lokhande, L., Bharti, N., Sachidanandan, C. (2022) BML-257, a Small Molecule that Protects against Drug-Induced Liver Injury in Zebrafish. Chemical Research in Toxicology. 35(8):1393-1399.
Abstract
The use of many essential drugs is restricted due to their deleterious effects on the liver. Molecules that can prevent or protect the liver from drug-induced liver injury (DILI) would be invaluable in such situations. We used a transgenic line in zebrafish with a hepatocyte-specific expression of bacterial nitroreductase to cause temporally controlled liver damage. A whole organism-based chemical screen using the transgenic line identified BML-257, a potent small molecule AKT inhibitor, that protected the liver against metronidazole-induced liver injury. BML-257 also showed potent prophylactic and pro-regenerative activity in this liver damage model. BML-257 was tested in two independent toxicological models of liver injury caused by acetaminophen and isoniazid and was found to be protective against damage. This suggests that BML-257 has the potential to protect against multiple kinds of DILI.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping