线粒体靶向抗氧化剂（MTAs）已知能够提供保护机制来对抗线粒体氧化应激。最近的证据支持了它们在缓解氧化应激诱导的疾病，包括癌症方面的作用。所以，本文研究了缓解5-FU诱导心肌毒性的Mito-TEMPO心脏保护潜力。Mito-TEMPO腹腔注射给BALB/C雄性小鼠（剂量为0.1mg/kg b.w.，连续7天），然后进行腹腔注射5-FU（剂量为12mg/kg b.w.，连续4天），并在此期间继续进行Mito-TEMPO处理。通过评价心脏损伤标志物、非活性心肌组织的程度和组织学改变来评估Mito-TEMPO的心脏保护潜力。还评估了心肌组织的线粒体功能状态和线粒体氧化应激，在免疫组化技术下评估了8-OHdG表达和凋亡细胞死亡情况。 心脏损伤标志物CK-MB和AST的水平在已给予Mito-TEMPO保护组中显著降低（P≤0.05），这在组织学中也反映为非活性心肌组织的比例降低、肌纤维失去有序排列。Mito-TEMPO改善了mtROS、mtLPO的水平并保持了线粒体膜电位。此外，它还显著（P≤0.05）提高了线粒体复合物和线粒体酶的活性。观察到mtGSH的水平增加、线粒体谷胱甘肽还原酶、谷胱甘肽过氧化物酶和线粒体超氧化物歧化酶的活性增加。给予Mito-TEMPO保护的组中观察到8-OHdG的表达下降和减少的凋亡细胞死亡。 Mito-TEMPO通过调节线粒体氧化应激有效地缓解5-FU诱导的心肌毒性，因此可能在基于5-FU的联合化疗中作为保护性剂或辅助治疗。© 2023. The Author(s).

The mitochondria-targeted antioxidants (MTAs) are known to offer protection against mitochondrial oxidative stress. The recent evidences support their role in mitigating oxidative stress-induced diseases, including cancer. Therefore, this study investigated cardioprotective potential of mito-TEMPO against 5-FU-induced cardiotoxicity.Mito-TEMPO was administered to male BALB/C mice (intraperitoneally, 0.1 mg/kg b.w. for 7 days) followed by intraperitoneal administration of 5- FU (12 mg/kg b.w. for 4 days). During this period, mito-TEMPO treatment was also continued. The cardioprotective potential of mito-TEMPO was assessed by evaluating cardiac injury markers, extent of non-viable myocardium and histopathological alterations. Mitochondrial functional status and mitochondrial oxidative stress were assessed in cardiac tissue. 8-OHdG expression and apoptotic cell death were assessed using immunohistochemical techniques.The level of cardiac injury markers CK-MB and AST were significantly (P ≤ 0.05) decreased in mito-TEMPO pre-protected group which was further reflected in histopathology as decrease in the percentage of non-viable myocardial tissue, disorganization, and loss of myofibrils. Mito-TEMPO ameliorated mtROS, mtLPO and conserved mitochondrial membrane potential. Further, it had significantly (P ≤ 0.05) improved the activity of mitochondrial complexes and mitochondrial enzymes. A significant (P ≤ 0.05) increase in the level of mtGSH, activity of mitochondrial glutathione reductase, glutathione peroxidase, and mitochondrial superoxide dismutase was observed. A decreased expression of 8-OHdG and reduced apoptotic cell death were observed in mito-TEMPO pre-protected group.Mito-TEMPO effectively mitigated 5-FU-induced cardiotoxicity by modulating mitochondrial oxidative stress, hence may serve as a protective agent/adjuvant in 5-FU-based combinatorial chemotherapy.© 2023. The Author(s).