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Allicin ameliorates doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis

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Abstract

Purpose

Doxorubicin (DOX) is a highly active antineoplastic agent; however, its clinical use is limited due to associated cardiotoxicity. This study was performed to evaluate the beneficial effects of allicin, a dietary garlic active constituent against DOX-induced cardiotoxicity.

Methods

Forty male Swiss albino mice were divided into five groups, which received normal saline, oral allicin (20 mg kg−1 once daily), intraperitoneal DOX (on the 7, 9 and 11th day of the experiment), or DOX plus once daily allicin at 10 or 20 mg kg−1. Sera were collected for evaluation of cardiac injury markers and proinflammatory cytokines. Additionally, heart tissue spacemen were harvested for determination of oxidative stress markers, as well as for histopathological examination and immunohistochemical analysis.

Results

DOX administration induced significant (p < 0.05) reductions in cardiac tissue level of reduced glutathione and activities of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). Moreover, it induced significant (p < 0.05) elevations in cardiac tissue concentrations of nitric oxide and malondialdehyde as well as serum levels of cardiac injury biomarkers (lactate dehydrogenase, creatine kinase, and creatine kinase-MB) and proinflammatory cytokines (interleukin-1β, and tumor necrosis factor-alpha). The histopathological examination showed necrotic and degenerative changes in the cardiac tissue, while immunohistochemical analysis revealed marked myocardial expression of activated caspase-3 and cyclooxygenase-2, following DOX adminstration. Allicin pretreatment significantly improved (p < 0.05) all examined parameters, and restored the cardiac architecture.

Conclusion

The current study demonstrated that allicin effectively mitigates cardiac oxidative damage, apoptosis and inflammation, induced by acute DOX intoxication. Therefore, allicin could be a promising cytoprotective agent against DOX cardiotoxicity.

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Abbreviations

CAT:

Catalase

CK:

Creatine kinase

CK-MB:

Creatine kinase-myocardial B fraction

COX2:

Cyclo-oxygenase-2

DOX:

Doxorubicin

GPx:

Glutathione peroxidase

GSH:

Glutathione

LDH:

Lactate dehydrogenase

IL-1β:

Interleukin-1β

MDA:

Malondialdehyde

NO:

Nitric oxide

8-OHdG:

8-Oxo-2′-deoxyguanosine

SOD:

Superoxide dismutase

TNF:

Tumor necrosis factor

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Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt

    Mohamed M. Abdel-Daim

  2. Department of Clinical Pathology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt

    Omnia E. kilany

  3. Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt

    Hesham A. Khalifa

  4. Cytology and Histology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt

    Amal A. M. Ahmed

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  1. Mohamed M. Abdel-Daim
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  2. Omnia E. kilany
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  3. Hesham A. Khalifa
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  4. Amal A. M. Ahmed
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Correspondence to Mohamed M. Abdel-Daim.

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This research work received no funding from any organization.

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This manuscript include animal experiments, and the animal handling, housing and care, as well as the experimental protocol were approved by Animal Care and Ethics Review Committee at the Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt (The Approval No. 201609). This article does not contain any studies with human participants performed by any of the authors.

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Abdel-Daim, M.M., kilany, O.E., Khalifa, H.A. et al. Allicin ameliorates doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Cancer Chemother Pharmacol 80, 745–753 (2017). https://doi.org/10.1007/s00280-017-3413-7

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  • DOI: https://doi.org/10.1007/s00280-017-3413-7

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