Key result
Tiron blunts doxorubicin cytotoxicity in cardiomyoblasts by reducing oxidative stress and preserving mitochondria.
Why the study?
Doxorubicin clinical use is limited by cardiotoxicity driven mainly by ferroptosis and oxidative stress, and whether Tiron provides cardioprotection by inhibiting these pathways required investigation.
Does Tiron pretreatment prevent doxorubicin-induced cardiotoxicity in H9c2 rat cardiomyoblast cells?
Does Tiron pretreatment prevent doxorubicin-induced cardiotoxicity in H9c2 rat cardiomyoblast cells?
Tiron demonstrates potential as a cardioprotective agent against doxorubicin-induced cardiotoxicity in vitro by inhibiting ferroptosis and apoptosis pathways and preserving mitochondrial function.
Tiron shows mechanistic promise in vitro; leaves open clinical translation for doxorubicin cardiotoxicity.
Doxorubicin (DOX) clinical use is limited by cardiotoxicity, mainly driven by ferroptosis and oxidative stress. Tiron, an antioxidant and iron chelator, may deliver cardioprotective effects by inhibiting these pathways. Thus, the present study aimed to examine the mechanistic effects of Tiron on ferroptosis and apoptosis in DOX-induced cardiotoxicity. H9c2 cardiomyocytes were pretreated with Tiron (0.1, 0.2, 0.5, and 1 mM) for 24 h prior to exposure to doxorubicin (1 µM) for an additional 24 h. Cell viability, DNA damage (comet assay), mitochondrial membrane potential (MMP), and membrane damage (lactate dehydrogenase [LDH] release) were assessed. Oxidative stress and ferroptosis markers, including GSH, ROS, SOD, MDA, GPX, and GPX4, were measured. Apoptosis was examined via caspase-3/7 activity and TUNEL assays. Tiron significantly improved viability, reduced LDH release, and lowered DNA fragmentation. It decreased MDA and ROS levels while restoring SOD, GPX, and GSH. Crucially, Tiron (1 mM) significantly restored cellular GPX4 levels suppressed by DOX. Tiron preserved MMP, indicating protection against mitochondrial dysfunction. Moreover, it attenuated caspase-3/7 activation and reduced apoptosis in the TUNEL assay. Tiron mitigates DOX-induced cardiotoxicity by modulating pathways associated with ferroptosis, apoptosis, and oxidative stress. Tiron demonstrates strong potential as a cardioprotective agent against anthracycline-induced injury by preserving mitochondrial function.
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Motafeghi et al. (2026) studied Doxorubicin-induced cardiotoxicity. Tiron vs. Doxorubicin alone was evaluated on Cell viability (p=<0.0001). Tiron pretreatment significantly mitigated doxorubicin-induced cytotoxicity in H9c2 cardiomyoblasts by reducing oxidative stress, preserving mitochondrial function, and inhibiting both ferroptosis and apoptosis.
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