Aidi injection reduces doxorubicin-induced cardiotoxicity by inhibiting carbonyl reductase 1 expression

Figures

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  Figure 1.. The scheme of experiment grouping and treatments in vivo.

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  Figure 2.. H&E staining images of heart tissues in mice treated with DOX (0.03 mg/10 g) and/or ADI (0.1 and 0.2 mL/10 g) (100× magnification). Cells in the control group were in good condition and neatly arranged. In the DOX treatment group, myocardial cell disorders and increased cellular gaps were observed. In the ADI treatment group, no significant changes in cell morphology were seen. In the DOX combined with ADI group, injuries to the cells were slightly reduced.

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  Figure 3.. The concentrations of CK, CK-MB, AST and LDH in the serum of mice treated with DOX (0.03 mg/10 g) and/or ADI (0.1 and 0.2 mL/10 g). Data are presented as mean ± SD (n = 6). *P < 0.05, ***P < 0.001 vs. control group without DOX treatment; #P < 0.05, ##P < 0.01, ###P < 0.001 vs. control group with DOX treatment.

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  Figure 4.. The concentration of BNP in the serum of mice treated with DOX (0.03 mg/10 g) and/or ADI (0.2 mL/10 g). Data are presented as mean ± SD (n = 6). ***P < 0.001 vs. control group without DOX treatment; ##P < 0.01, ###P < 0.001 vs. control group with DOX treatment.

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  Figure 5.. Concentrations of DOX and DOXol in the serum, heart, liver, and kidneys of mice treated with DOX alone or combined with ADI. DOX (A) and DOXol (B) concentrations in mice serum. DOX (C) and DOXol (D) concentrations in heart. DOX (E) and DOXol (F) concentrations in liver. DOX (G) and DOXol (H) concentrations in kidneys. Values are presented as mean ± SD (n = 6). *P < 0.05, **P < 0.01, ***P < 0.001 vs. single-dose administration of DOX; ##P < 0.01, ###P < 0.001 vs. multiple-dose administration of DOX.

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  Figure 6.. The protective effects of ADI on DOX-induced cytotoxicity in H9c2 cells. (A) Logarithmic plots of the inhibition curves obtained after treating the cells with DOX (1, 5, 10, 20, 50 and 100 μM) in the presence or absence of ADI (1, 4, 10%). (B) Effect of ADI on caspase-3 activity induced by DOX (5 μM) in H9c2 cells. (C) Representative fluorescence images of Hoechst 33342 staining of H9c2 cells after different treatments. Magnification: 200× Values are expressed as mean ± SD from six independent experiments. **P < 0.01, ***P < 0.001 vs. control group without DOX, ###P < 0.001 vs. control group with DOX.

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  Figure 7.. Time-concentration curves of DOX (A) and DOXol (B) in H9c2 cells. H9c2 cells were incubated with 5 μM DOX in the absence or presence of 1, 4, or 10% ADI for 1, 2, 4, 8, 12 and 18 h. DOX and DOXol concentrations in cells were quantified by UPLC-MS/MS. Data are expressed as mean ± SD of six independent experiments. **P < 0.01, ***P < 0.001 vs. DOX group at the same time.

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  Figure 8.. Effects of ADI on the expression of CBR1 in H9c2 cells. H9c2 cells were incubated with ADI (10%) or an equivalent volume of PBS for 18 h. CBR1 protein levels was determined by western blot analysis. (A) Representive images of CBR1 expression detected by Western blotting. (B) Protein ratios normalised to GAPDH used to quantify fold change by densitometry and shown in a histogram. Data are expressed as mean ± SD of three independent experiments. **P < 0.01 vs. control group at the same time.