PUBLICATION

Lansoprazole Ameliorates Isoniazid-Induced Liver Injury

Authors
Wakai, E., Shiromizu, T., Otaki, S., Koiwa, J., Tamaru, S., Nishimura, Y.
ID
ZDB-PUB-240123-13
Date
2024
Source
Pharmaceuticals (Basel, Switzerland)   17(1): (Journal)
Registered Authors
Nishimura, Yuhei
Keywords
FDA adverse event reporting system, connectivity map, drug repositioning, drug-induced liver injury, electronic health records, gene expression signature, zebrafish
MeSH Terms
none
PubMed
38256915 Full text @ Pharmaceuticals (Basel)
Abstract
Isoniazid is a first-line drug in antitubercular therapy. Isoniazid is one of the most commonly used drugs that can cause liver injury or acute liver failure, leading to death or emergency liver transplantation. Therapeutic approaches for the prevention of isoniazid-induced liver injury are yet to be established. In this study, we identified the gene expression signature for isoniazid-induced liver injury using a public transcriptome dataset, focusing on the differences in susceptibility to isoniazid in various mouse strains. We predicted that lansoprazole is a potentially protective drug against isoniazid-induced liver injury using connectivity mapping and an adverse event reporting system. We confirmed the protective effects of lansoprazole against isoniazid-induced liver injury using zebrafish and patients' electronic health records. These results suggest that lansoprazole can ameliorate isoniazid-induced liver injury. The integrative approach used in this study may be applied to identify novel functions of clinical drugs, leading to drug repositioning.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping