Resveratrol significantly improves cell....pdf (4.65 MB)

Resveratrol significantly improves cell survival in comparison to dexrazoxane and carvedilol in a h9c2 model of doxorubicin induced cardiotoxicity

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journal contribution
posted on 26.05.2021, 15:46 by David S Monahan, Eimhear Flaherty, Aamir Hameed, Garry Duffy
Cancer is one of the leading causes of deaths worldwide with 18.1 million deaths per year. Although there have been significant advances in anti-cancer therapies, they can often result in side effects with cardiovascular complications being the most severe. Dexrazoxane is the only currently approved treatment for prevention of anthracycline induced cardiotoxicity but there are concerns about its use due to the development of secondary malignancies and myelodysplastic syndrome. Additionally, it is only recommended in patients who are due to receive a total cumulative dose of 300 mg/m2 of doxorubicin or 540 mg/m2 of epirubicin. Thus, there exists an urgent need to develop new therapeutic strategies to counteract anthracycline induced cardiotoxicity. The h9c2 cardiomyoblast was investigated for its differentiation capacity and used to screen and compare promising prophylactics for doxorubicin induced cardiotoxicity. The half maximal inhibitory concentration of doxorubicin was determined in differentiated h9c2 cells after 24 h of exposure, to establish a model for drug screening. Cells were treated with dexrazoxane, resveratrol, and carvedilol either 3 h or 24 h prior to doxorubicin treatment. The ability of these cardioprotectants to prevent cardiotoxicity was analysed using the cck-8 cell viability assay and the dichlorofluorescin diacetate (DCFDA) reactive oxygen species (ROS) assay. There was no significant increase in survival in treatment groups after 3 h, however, at 24 h, resveratrol significantly improved survival compared to all other groups (p < 0.05). Additionally, dexrazoxane and resveratrol significantly decreased ROS formation at 3 h (p < 0.05) and all groups significantly decreased ROS production at 24 h (p < 0.001). This work is the first comparison of these cardioprotectants and suggests that resveratrol may be a more effective treatment in the prevention of anthracycline induced cardiotoxicity, compared to dexrazoxane and carvedilol. However, further work will be needed in order to decipher the exact mechanism and potential of this drug in the clinic.

Funding

Cancer therapy-induced cardiotoxicities

Irish Research Council Government of Ireland Postgraduate Scholarship (GOIPG/2017/927)

Fulbright Enterprise Ireland Program, Ireland-USA

History

Comments

The original article is available at https://www.sciencedirect.com

Published Citation

Monahan DS, Flaherty E, Hameed A, Duffy GP. Resveratrol significantly improves cell survival in comparison to dexrazoxane and carvedilol in a h9c2 model of doxorubicin induced cardiotoxicity. Biomed Pharmacother. 2021;140:111702.

Publication Date

17 May 2021

PubMed ID

34015579

Department/Unit

  • Anatomy and Regenerative Medicine
  • RCSI Tissue Engineering Group (TERG)

Research Area

  • Surgical Science and Practice
  • Biomaterials and Regenerative Medicine

Publisher

Elsevier

Version

  • Published Version (Version of Record)