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Curcumin attenuates bevacizumab-induced toxicity via suppressing oxidative stress and preventing mitochondrial dysfunction in heart mitochondria

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Abstract

Heart failure was subsequently noted in 2–4% of patients on bevacizumab (BEV). Whereas mitochondria play an important role in myocardial tissue homeostasis, deterioration in mitochondrial function will eventually lead to cardiomyocyte cell death and consequently cardiovascular dysfunction. Therefore, the aim of our study is to search the effects of BEV on isolated rat heart mitochondria and cardiomyocytes, and survey the effect of curcumin as a mitochondrial protective and cardioprotective agent. Rat heart mitochondria and cardiomyocytes were isolated from adult rat heart ventricular. By using biochemical and flow cytometry evaluations, the parameters of mitochondrial toxicity including succinate dehydrogenase (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP) collapse, reactive oxygen species (ROS) formation and lipid peroxidation (LP), and cellular assays such as cytotoxicity and MMP collapse were evaluated. Results revealed that BEV (up to 50 μg/ml) induced a concentration- and time-dependent rise in mitochondrial ROS formation, MMP collapse, mitochondrial swelling, LP, and inhibition of SDH in rat heart mitochondria. Our results showed that curcumin (10–100 μM) significantly ameliorated BEV-induced mitochondrial toxicities. Also, our results in cellular assays confirmed amelioration effect of curcumin against BEV toxicity. These results indicate that the cardiotoxic effects of BEV are associated with mitochondrial dysfunction and ROS formation, which finally ends in MMP collapse and mitochondrial swelling as the “point of no return” in the cascade of events leading to apoptosis. Also, results of this study suggest that probably the combination therapy of BEV and curcumin could decrease mitochondrial effects of this drug.

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Acknowledgments

The data provided in this article was extracted from the Pharm D. thesis of Dr. Nima Shokouhi Sabet. The thesis was conducted under supervision of Dr. Ahmad Salimi at the Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran. This study was supported by Ardabil of Medical Sciences, Deputy of Research.

Author contribution statement

AS conceived and designed the research, analyzed the data, and wrote the manuscript. NS, SA, and EM conducted the experiments. FK contributed new reagents or analytical tools. All authors read and approved the manuscript.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, P.O. Box: 56189-53141, Ardabil, Iran

    Nima Shokouhi Sabet, Saman Atashbar, Elham Mohammad Khanlou & Ahmad Salimi

  2. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Damghan Islamic Azad University, Damghan, Iran

    Farzad Kahrizi

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  1. Nima Shokouhi Sabet
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  2. Saman Atashbar
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Correspondence to Ahmad Salimi.

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This study was approved by the Ethics Committee at the Ardabil University of Medical Sciences  with ethics code IR.ARUMS.REC.1397.293, and performed strictly in accordance with institutional and international guide for animal care.

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Sabet, N.S., Atashbar, S., Khanlou, E.M. et al. Curcumin attenuates bevacizumab-induced toxicity via suppressing oxidative stress and preventing mitochondrial dysfunction in heart mitochondria. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1447–1457 (2020). https://doi.org/10.1007/s00210-020-01853-x

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