Key result
Thymoquinone protected against doxorubicin-induced cardiotoxicity and mitochondrial damage in mice by activating the Nrf2/HO-1 signaling pathway to alleviate ferroptosis.
Why the study?
Ferroptosis is a key process in doxorubicin-induced cardiotoxicity and a potential therapeutic target, prompting investigation into the protective effects and mechanisms of thymoquinone.
RCT
randomly assigned
Answers are grounded in this paper and cite their sources.
Should not change doxorubicin cardioprotection practice; hypothesis-generating for TQ in ferroptosis-mediated cardiotoxicity.
BACKGROUND: Ferroptosis is a key process in doxorubicin (DOX)-induced cardiotoxicity and is a potentially important therapeutic target. Thymoquinone (TQ) is a monoterpenoid compound isolated from black cumin extract that exhibits antitumor effects and acts as a powerful mitochondrial-targeted antioxidant. In this study, we investigated the effect of TQ on DOX-induced cardiotoxicity and the potential underlying mechanisms. METHODS AND RESULTS: Mice were randomly assigned to the control (CON) group, DOX (20 mg/kg) group, TQ10 (10 mg/kg/d) group, and TQ20 (20 mg/kg/d) group and intraperitoneally injected with DOX and different doses of TQ. The electrocardiogram, blood pressure, and cardiac ultrasound changes during the experiments showed that TQ exerted a protective effect against DOX-induced cardiotoxicity. The glutathione (GSH), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) levels in the mouse heart tissue were significantly different from those in the CON group. Western blot analysis revealed that the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) in the DOX group was lower than that in the control group. TQ treatment decreased these changes, indicating that TQ alleviated DOX-induced cardiotoxicity and increased the antioxidant capacity of murine cardiomyocytes. The mechanism might involve activating the Nrf2/HO-1 signaling pathway and reducing iron-mediated death. Immunohistochemical staining revealed similar effects on the expression levels of NQO1, COX-2, and NOX4. Moreover, transmission electron microscopy indicated that TQ protected murine cardiomyocytes against DOX-induced mitochondrial damage. CONCLUSION: The results of this study suggested that TQ can decrease oxidative stress levels and DOX-induced cardiotoxicity by activating the Nrf2/HO-1 signaling pathway to alleviate ferroptosis in murine cardiomyocytes.
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Chen et al. (2024) conducted an RCT in doxorubicin-induced cardiotoxicity. Thymoquinone (TQ) vs. Control and DOX alone was evaluated on Cardiotoxicity and oxidative stress markers. Thymoquinone protected against doxorubicin-induced cardiotoxicity and mitochondrial damage in mice by activating the Nrf2/HO-1 signaling pathway to alleviate ferroptosis.
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