Mitigation of Senescence Burden in Doxorubicin-Induced Senescent Endothelial Cells by MitoQ Treatment Through Diminishing Mitochondrial ROS and DNA Damage.
<p dir="ltr">Chemotherapy-induced cardiovascular toxicity is a major clinical concern, particularly with agents like doxorubicin (DOXO), which elevate mitochondrial reactive oxygen species (mtROS) and induce endothelial cell (EC) dysfunction and senescence. This study investigates wh...
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2025
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| Summary: | <p dir="ltr">Chemotherapy-induced cardiovascular toxicity is a major clinical concern, particularly with agents like doxorubicin (DOXO), which elevate mitochondrial reactive oxygen species (mtROS) and induce endothelial cell (EC) dysfunction and senescence. This study investigates whether co-treatment with MitoQ, a mitochondria-targeted antioxidant, attenuates DOXO-induced endothelial damage. Using primary human umbilical vein endothelial cells (HUVECs), we assessed mitochondrial superoxide levels, mitochondrial mass, DNA damage, senescence markers (p21, p16, SA-βgal), proliferation (BrdU), and telomere dysfunction (TIFs) after 48 hours of treatment with DOXO, MitoQ, or both. DOXO increased mtROS, decreased mitochondrial mass, and induced senescence. Co-treatment with MitoQ significantly reduced mtROS, preserved mitochondrial mass, and mitigated DNA damage and senescence phenotypes. Our findings support a mechanistic model in which mtROS promotes EC senescence via DNA and telomere damage. MitoQ prevents these effects, providing foundational evidence for its potential use as a vascular-protective agent in chemotherapy patients. These results align with prior in vivo studies and suggest a rationale for translational investigation.</p> |
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