Propofol protects cardiomyocytes from doxorubicin-induced toxic injury by activating the nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 signaling pathways

Figures

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  Figure 1.. Propofol alleviates DOX-induced cytotoxicity and activates Nrf2/GPx4 signaling pathway in H9c2 cells. (a) Relative cell viability of H9c2 cells in the groups of control, DOX, DOX+Prop (5, 10, 20 μM) was examined at 24 h by CCK-8. ***P < 0.001. (b) The level of LDH in the groups of control, DOX, DOX+Prop (5, 10, 20 μM) was detected by LDH assay kit. ***P < 0.001. (c-d) The protein levels of Nrf2 (nuclear), Nrf2 (cytoplasm), Keap1 and GPx4 in H9c2 cells were measured by Western blot in the groups of control, DOX, DOX+Prop (5, 10, 20 μM). *P < 0.05, **P < 0.01, ***P < 0.001.

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  Figure 2.. Propofol attenuates DOX-induced ferroptosis in H9c2 cells by activating Nrf2/GPx4 signaling pathway. (a) The content of Fe2+ in H9c2 cells was assessed by the commercial kit in the groups of control, DOX, DOX+Prop (5, 10, 20 μM). ***P < 0.001. (b-c) The protein levels of PTGS2, Ferritin and ASCL4 related to ferroptosis in H9c2 cells were detected by Western blot in the groups of control, DOX, DOX+Prop (5, 10, 20 μM). **P < 0.01, ***P < 0.001.

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  Figure 3.. Propofol promotes DOX-induced viability and inhibits apoptosis in H9c2 cells through the activation of Nrf2/GPx4 signaling pathway. (a) Relative cell viability of H9c2 cells was measured by CCK-8 in the groups of control, DOX, DOX+Prop and DOX+Prop+ML385. *P < 0.05, ***P < 0.001. (b-c) Cell apoptosis rate of H9c2 cells was examined by TUNEL in the groups of control, DOX, DOX+Prop and DOX+Prop+ML385. ***P < 0.001. (d) Protein levels of Bax, Bad and Bcl-2 related to apoptosis were tested by Western blot of H9c2 cells was measured by CCK-8 in the groups of control, DOX, DOX+Prop and DOX+Prop+ML385. **P < 0.01, ***P < 0.001.

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  Figure 4.. Propofol inhibits DOX-induced oxidative stress in H9c2 cells via the activation of Nrf2/GPx4 signaling pathway. (a) ROS level of H9c2 cells was determined by DCFH-DA kit in the groups of control, DOX, DOX+Prop and DOX+Prop+ML385. ***P < 0.001. (b-d) The levels of MDA, GSH and 4-HNE were measured by the corresponding commercial kits in the groups of control, DOX, DOX+Prop and DOX+Prop+ML385. ***P < 0.001.

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  Figure 5.. Propofol inhibits DOX-induced inflammatory response in H9c2 cells via activating Nrf2/GPx4 signaling pathway. (a-c) The levels of TNF-α, IL-6, IL-1β were examined by ELISA assay in the groups of control, DOX, DOX+Prop and DOX+Prop+ML385. ***P < 0.001. (d) Protein levels of p-p65 and p65 were assessed by Western blot in the groups of control, DOX, DOX+Prop and DOX+Prop+ML385. ***P < 0.001.