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The Protective Effects of Coenzyme Q10 and Lisinopril Against Doxorubicin-Induced Cardiotoxicity in Rats: A Stereological and Electrocardiogram Study

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Abstract

Doxorubicin (DOX) is used as an anticancer drug despite its several side effects, especially its irreversible impacts on cardiotoxicity. Coenzyme Q10 (Q10) as a powerful antioxidant and lisinopril (LIS) as an angiotensin-converting enzyme inhibitor seem to provide protection against DOX-induced cardiotoxicity. Therefore, this study aimed to assess the cardioprotective effects of Q10 and LIS against DOX-induced cardiotoxicity in rats. Adult male Sprague–Dawley rats were randomly assigned into the control, LIS, Q10, DOX, DOX + LIS, and DOX + Q10 groups. On day 21, ECG was recorded and the right ventricle was dissected for evaluation of catalase activity and malondialdehyde (MDA) concentration. Additionally, the left ventricle and the sinoatrial (SA) node were dissected to assess the stereological parameters. The results of ECG indicated bradycardia and increase in QRS duration and QT interval in the DOX group compared to the control group. Meanwhile, the total volumes of the left ventricle, myocytes, and microvessels and the number of cardiomyocyte nuclei decreased, whereas the total volume of the connective tissue and the mean volume of cardiomyocytes increased in the DOX group. On the other hand, the SA node and the connective tissue were enlarged, while the volume of the SA node nuclei was reduced in the DOX group. Besides, catalase activity was lower and MDA concentration was higher in the DOX‐treated group. Q10 could recover most stereological parameters, catalase activity, and MDA concentration. LIS also prevented some stereological parameters and ECG changes and improved catalase activity and MDA concentration in the DOX group. The findings suggested that Q10 and LIS exerted cardioprotective effects against DOX-induced cardiac toxicity.

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Acknowledgements

This research was a part of Maryam Rahmanifard’s M.Sc. thesis in Biochemistry and was financially supported by Grant No. 16330520952001 from Islamic Azad University, Shiraz Branch. Hereby, the authors would like to thank Ms. A. Keivanshekouh at the Research Improvement Center of Shiraz University of Medical Sciences for improving the use of English in the manuscript.

Funding

This research was supported by Islamic Azad University, Shiraz branch, Shiraz, Iran (Funding No. 16330520952001).

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Authors and Affiliations

  1. Department of Biology, Islamic Azad University, Shiraz Branch, Shiraz, Iran

    Maryam Rahmanifard & Mahmood Vessal

  2. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Zand Ave., 71348-45794, Shiraz, Iran

    Ali Noorafshan, Saied Karbalay-Doust & Maryam Naseh

  3. Department of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Noorafshan & Saied Karbalay-Doust

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  1. Maryam Rahmanifard
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Correspondence to Saied Karbalay-Doust or Maryam Naseh.

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All experimental procedures were approved by the Medical and Research Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran (Approval No. 16330520952001).

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Rahmanifard, M., Vessal, M., Noorafshan, A. et al. The Protective Effects of Coenzyme Q10 and Lisinopril Against Doxorubicin-Induced Cardiotoxicity in Rats: A Stereological and Electrocardiogram Study. Cardiovasc Toxicol 21, 936–946 (2021). https://doi.org/10.1007/s12012-021-09685-8

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