Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, mitigate doxorubicin-induced damage in H9c2 myoblast: pretreatment vs. co-treatment
| Autor: | Sachin Prasad, Rose Martorana, Erin Ross, Catherine Wastella, Robert Barsotti, Halil Onal, Hafsa Ahmad, Lindon H. Young, Adona Pjetergjoka, Amogh Sehgal, Amanda Harvey, Qian Chen, Brian Sacks |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Antioxidant
Cardiotonic Agents Cell Survival Plastoquinone Ubiquinone medicine.medical_treatment RM1-950 Ascorbic Acid Pharmacology medicine.disease_cause Antioxidants Drug Administration Schedule Cell Line chemistry.chemical_compound Organophosphorus Compounds Superoxides RA1190-1270 medicine Animals Pharmacology (medical) Doxorubicin Drug Interactions Myocytes Cardiac Viability assay Vitamin C Cardioprotection Cardiotoxicity MitoQ Antibiotics Antineoplastic Chemistry Mitochondria Rats Oxidative stress Toxicology. Poisons Mitochondrial-targeted antioxidants Therapeutics. Pharmacology medicine.drug Research Article |
| Zdroj: | BMC Pharmacology & Toxicology BMC Pharmacology and Toxicology, Vol 22, Iss 1, Pp 1-16 (2021) |
| ISSN: | 2050-6511 |
| Popis: | Background Preconditioning of the heart ameliorates doxorubicin (Dox)-induced cardiotoxicity. We tested whether pretreating cardiomyocytes by mitochondrial-targeted antioxidants, mitoquinone (MitoQ) or SKQ1, would provide better protection against Dox than co-treatment. Methods We investigated the dose-response relationship of MitoQ, SKQ1, and vitamin C on Dox-induced damage on H9c2 cardiomyoblasts when drugs were given concurrently with Dox (e.g., co-treatment) or 24 h prior to Dox (e.g., pretreatment). Moreover, their effects on intracellular and mitochondrial oxidative stress were evaluated by 2,7-dichlorofluorescin diacetate and MitoSOX, respectively. Results Dox (0.5–50 μM, n = 6) dose-dependently reduced cell viability. By contrast, co-treatment of MitoQ (0.05–10 μM, n = 6) and SKQ1 (0.05–10 μM, n = 6), but not vitamin C (1–2000 μM, n = 3), significantly improved cell viability only at intermediate doses (0.5–1 μM). MitoQ (1 μM) and SKQ1 (1 μM) significantly increased cell viability to 1.79 ± 0.12 and 1.59 ± 0.08 relative to Dox alone, respectively (both p n = 9) and SKQ1 (5 μM, n = 7) showed maximal protection and improved cell viability to 2.19 ± 0.13 and 1.65 ± 0.07 relative to Dox alone, respectively (both p Conclusion The data suggest that MitoQ and SKQ1, but not vitamin C, mitigated DOX-induced damage. Moreover, MitoQ pretreatment showed significantly higher cardioprotection than its co-treatment and SKQ1, which may be due to its better antioxidant effects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink