Article Figures & Data
Figures
- Fig. 1.
Metabolomic analysis of mouse liver from the control and INH-treated groups. Wild-type mice were treated with vehicle or 200 mg/kg INH (by mouth). Liver samples were collected 30 minutes after treatment. All samples were analyzed by UPLC-QTOFMS. (A) Separation of control and INH-treated groups in a PCA score plot. The t[1] and t[2] values represent the score of each sample in principal components 1 and 2, respectively. (B) Loading S-plot generated by orthogonal projection to latent structures discriminant analysis. w[1]P, measure of the relative abundance of ions; p(corr)[1]P, measure of the correlation of each ion to the model.
- Fig. 2.
Accumulation of heme (I) in the livers of mice treated with INH. (A) The extracted chromatogram of heme. (B) MS/MS findings of heme. (C) Relative abundance of heme. The data are expressed as the mean ± SEM (n = 3). ***p < 0.001 versus control group.
- Fig. 3.
Accumulation of oleoyl-l-carnitine (II) and linoleoyl-l-carnitine (metabolite III) in the livers of mice treated with INH. (A) Extracted chromatograms of acylcarnitines II and III. (B) MS/MS findings of oleoyl-l-carnitine (II). (C) MS/MS findings of linoleoyl-l-carnitine (III). (D) Relative abundance of acylcarnitines II and III in the liver. The data are expressed as the mean ± SEM (n = 3). **p < 0.01, ***p < 0.001 versus control group.
- Fig. 4.
Formation of INH-fatty acid amides (IV and V). (A) Extracted chromatograms of amides IV and V. (B) MS/MS findings of amide IV. (C) MS/MS findings of amide V. (D) Relative abundance of amides IV and V. The data are expressed as the mean ± SEM (n = 3). **p < 0.01 versus control group. (E) The scheme of the formation of INH-fatty acid amides. N.D., not detected.
- Fig. 5.
Accumulation of NAD (VI) in the livers of mice treated with INH. (A) MS/MS findings of NAD. (B) Relative abundance of NAD in the liver. The data are expressed as the mean ± SEM (n = 3). ***p < 0.001 versus control group. (C) The inhibitory effect of INH on NADase activity.
- Fig. 6.
Formation of INH-NAD adduct (VII) in the livers of mice treated with INH. (A) MS/MS findings of INH-NAD adduct. (B) MS/MS findings of d4-INH-NAD adduct. (C) Relative abundance of INH-NAD adduct in the liver. (D) The role of NADase in the formation of INH-NAD adduct. The quantified data are expressed as the mean ± SEM (n = 3). N.D., not detected. ***p < 0.001 versus control group.
- Fig. 7.
Accumulation of cystathionine (VIII) in the livers of mice treated with INH. (A) The extracted chromatogram of cystathionine from the liver. (B) MS/MS findings of cystathionine. (C) Relative abundance of cystathionine in the liver. (D) MS/MS findings of INH-PL adduct. (E) Relative abundance of PLP in the liver. All quantified data are expressed as the mean ± SEM (n = 3). **p < 0.01, ***p < 0.001 versus control group. (F) The proposed mechanism by which INH disturbs cystathionine homeostasis. CSE, cystathionine gamma-lyase.
- Fig. 8.
The scheme of disturbance of endogenous pathways in mouse liver by a high dose of INH. FA, fatty acid.
Additional Files
Data Supplement
Files in this Data Supplement:
- Supplemental Data -
Supplemental Table 1 - The top ranking ions in the serum of mice treated with INH
Supplemental Figure 1 - Metabolomic analysis of mouse serum from the control and INH-treated groups
Supplemental Figure 2 - Biochemical analysis of serum ALT (A) and AST (B) activities in mice treated with INH
- Supplemental Data -
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