Mitochondrial targeted antioxidants, mitoquinone and SKQ1, not vitamin C, mitigate doxorubicin-induced damage in H9c2 myoblast: pretreatment vs. co-treatment

Autor: Brian Sacks, Halil Onal, Rose Martorana, Amogh Sehgal, Amanda Harvey, Catherine Wastella, Hafsa Ahmad, Erin Ross, Adona Pjetergjoka, Sachin Prasad, Robert Barsotti, Lindon H. Young, Qian Chen
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: BMC Pharmacology and Toxicology, Vol 22, Iss 1, Pp 1-16 (2021)
Druh dokumentu: article
ISSN: 2050-6511
DOI: 10.1186/s40360-021-00518-6
Popis: Abstract 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
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