Key result
Mito-TEMPO pre-treatment reduces 5-FU-induced non-viable myocardium by ~70% and attenuates mitochondrial oxidative stress.
Why the study?
Mitochondria-targeted antioxidants mitigate mitochondrial oxidative stress, prompting investigation into the cardioprotective potential of mito-TEMPO against 5-fluorouracil-induced cardiotoxicity.
Does mito-TEMPO prevent 5-fluorouracil-induced cardiotoxicity in male BALB/C mice?
Does mito-TEMPO prevent 5-fluorouracil-induced cardiotoxicity in male BALB/C mice?
Absolute Event Rate: 11.37% vs 37.57%
p-value: p=≤0.05
Mito-TEMPO shows cardioprotective potential against 5-fluorouracil-induced cardiotoxicity in a mouse model by modulating mitochondrial oxidative stress.
Mito-TEMPO may attenuate 5-FU cardiotoxicity in mice; leaves open clinical translation and requires human trials before any practice change.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Tambe et al. (2023) studied 5-Fluorouracil-induced cardiotoxicity. Mito-TEMPO vs. 5-FU alone was evaluated on Area of non-viable myocardium (p=≤0.05). Mito-TEMPO pre-treatment significantly reduced the area of 5-FU-induced non-viable myocardium from 37.57% to 11.37% and attenuated mitochondrial oxidative stress.
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