アブストラクト | 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. |
ジャーナル名 | Pharmaceuticals (Basel, Switzerland) |
投稿日 | 2024/1/23 |
投稿者 | Wakai, Eri; Shiromizu, Takashi; Otaki, Shota; Koiwa, Junko; Tamaru, Satoshi; Nishimura, Yuhei |
組織名 | Department of Integrative Pharmacology, Mie University Graduate School of;Medicine, Tsu 514-8507, Mie, Japan.;Mie University Research Center for Cilia and Diseases, Tsu 514-8507, Mie, Japan.;Clinical Research Support Center, Mie University Hospital, Tsu 514-8507, Mie,;Japan. |
Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38256915/ |