Sodium thiosulfate prevents doxorubicin-induced DNA damage and apoptosis in cardiomyocytes in mice

Yukie Mizuta, Kentaro Tokuda, Jie Guo, Shuo Zhang, Sayoko Narahara, Takahito Kawano, Masaharu Murata, Ken Yamaura, Sumio Hoka, Makoto Hashizume, Tomohiko Akahoshi

研究成果: Contribution to journalArticle査読

7 被引用数 (Scopus)

抄録

AIM: Doxorubicin (DOX) induces dose-dependent cardiotoxicity due to reactive oxygen species (ROS)-mediated oxidative stress and subsequent apoptosis of cardiomyocytes. We aimed to assess whether sodium thiosulfate (STS), which has antioxidant and antiapoptotic properties, exerts cardioprotective effects on DOX-induced cardiomyopathy.

MAIN METHODS: Male C57BL/6N mice were divided into four groups, control, DOX, STS, and DOX + STS, and administered DOX (20 or 30 mg/kg) or normal saline intraperitoneally, followed by an injection of STS (2 g/kg) or normal saline 4 h later.

KEY FINDINGS: The DOX group showed a poorer 6-day survival and decreased cardiac function than the DOX + STS group. The DOX group showed a marked increase in the plasma creatine kinase isoenzyme myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels 10 h after DOX injection, while the DOX + STS group showed suppression of DOX-induced elevation of CK-MB and LDH levels. The DOX group showed increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the heart, whereas the DOX + STS group showed increased catalase and superoxide dismutase (SOD) activities and decreased 8-OHdG levels in the heart compared with DOX group, suggesting that STS reduces DOX-induced DNA damage by improving antioxidant enzymes activities in cardiomyocytes. Additionally, the DOX + STS group showed attenuation of cleaved caspase-3 and DNA fragmentation in cardiomyocytes compared with the DOX group, suggesting that STS suppresses DOX-induced apoptosis in cardiomyocytes.

SIGNIFICANCE: STS exerts cardioprotective effects against DOX-induced cardiac dysfunction partly by improving antioxidant defense and suppressing apoptosis, indicating the therapeutic potential of STS against DOX-induced cardiomyopathy.

本文言語英語
ページ(範囲)118074
ジャーナルLife Sciences
257
早期オンライン日7 13 2020
DOI
出版ステータス印刷前のE-pub - 7 13 2020

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