Comparative transcriptome analysis of the mouse livers that were susceptible or resistant to IILI. (A–D) Venn diagrams of unique and shared differentially expressed genes in untreated vs. INH-treated mouse livers that were susceptible (A,B) or resistant (C,D) to IILI. Differentially expressed genes were identified using a false discovery rate threshold of 30%. (A,C) show genes that were upregulated, whereas (B,D) show genes that were downregulated by the INH treatment. (E,F) Venn diagrams of genes that were upregulated (E) or downregulated (F) in at least two strains among those susceptible or resistant to IILI.

Identification of lansoprazole as a protectant against IILI using in silico and in vivo analyses. (A) Clue identified chemicals that potentially caused patterns opposite to those of the IILI-GES. The search for inverse signals via the FAERS identified clinical drugs that potentially worked against IILI. Thirteen clinical drugs were common in the three groups, including lansoprazole (LPZ). (B) In vivo fluorescence imaging of livers of a transgenic zebrafish line Tg (pck1: tagGFP-DEVD-tagRFP) at 5 dpf exposed to INH (6 mM for 24 h) with and without LPZ (10 or 50 μM for 24 h). (C) Hepatic apoptosis was assessed as the ratio of fluorescence signals through narrow and wide filters of the liver of zebrafish exposed to INH with or without LPZ. Black circles represent individual zebrafish, and bars represent the group medians. n = 10 for each group. * p < 0.05, ** p < 0.01. (D) The expression of tnfa in zebrafish exposed to INH with or without LPZ was assessed using quantitative PCR analysis. Black circles represent individual zebrafish, and bars represent the group medians. n = 4 for control and INH only, and n = 3 for INH with LPZ. * p < 0.05, ** p < 0.01.