Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction

Figures

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  Figure 1. Toxic effect of cisplatin on the viability of rat cardiomyocytes and protective effects of TMZ and CoQ10. (a) Cell viability upon cisplatin (50 to 800 µM) treatment for 24 h. (b) Cell viability upon 200 µM cisplatin treatment for different periods of time (0, 6, 12, 24, and 48 h). (c) Cell viability in control, cisplatin, cisplatin+TMZ, cisplatin+CoQ10, and cisplatin+TMZ+CoQ10 groups. Data were normalized to that of control (assigned as a value of 1) and presented as mean±SD. ***P<0.001 as compared with control; ##P<0.01, and ###P<0.001 as compared with cisplatin-treated cells; and $P<0.05 as compared with TMZ or CoQ10-pretreated cells TMZ - trimetazidine; CoQ10 - coenzyme Q10

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  Figure 2. TMZ and CoQ10 reduced cisplatin-induced cardiomyocyte apoptosis. (a) Representative scatter plot of cell apoptosis in control, cisplatin, cisplatin+TMZ, cisplatin+CoQ10, and cisplatin+TMZ+CoQ10 groups. (b) Apoptotic rates presented as mean±SD. ***P<0.001 as compared with control; ###P<0.001 as compared with cisplatin-treated cells; and $P<0.05 as compared with TMZ or CoQ10-pretreated cells TMZ - trimetazidine; CoQ10 - coenzyme Q10

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  Figure 3. TMZ and CoQ10 enhanced nuclear Nrf2 expression in cisplatin-treated cells. Representative images of nuclear and cytosolic Nrf2 expression. GAPDH and Lamin A were used as the internal controls of cytosolic and nuclear fractions, respectively TMZ - trimetazidine; CoQ10 - coenzyme Q10

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  Figure 4. TMZ and CoQ10 attenuated cisplatin-induced ΔΨm dysfunction in cardiomyocytes. (a) Representative images of JC-1 staining. (b) Quantitative analysis of JC-1 staining presented as mean±SD. ***P<0.001 as compared with control; #P<0.05 and ###P<0.001 as compared with cisplatin-treated cells; and $P<0.05 as compared with TMZ or CoQ10-pretreated cells TMZ - trimetazidine; CoQ10 - coenzyme Q10

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  Figure 5. TMZ and CoQ10 suppressed the release of cyto-c into cytosol in cisplatin-treated cells. Representative images of mitochondrial and cytosolic cyto-c expression. GAPDH and COX IV served as the internal controls of cytosolic and mitochondrial fractions, respectively TMZ - trimetazidine; CoQ10 - coenzyme Q10