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

• Published in: Cancer chemotherapy and pharmacology Vol. 80; no. 4; pp. 745 - 753
• Main Authors: Abdel-Daim, Mohamed M., kilany, Omnia E., Khalifa, Hesham A., Ahmed, Amal A. M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2017; Springer Nature B.V
• Subjects: Animals; Antibiotics, Antineoplastic - toxicity; Antioxidants; Antioxidants - administration & dosage; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Biomarkers; Biomarkers - blood; Cancer Research; Cardiotoxicity; Cardiotoxicity - etiology; Cardiotoxicity - prevention & control; Caspase; Caspase-3; Catalase; Creatine; Creatine kinase; Cyclooxygenase-2; Cytokines; Cytokines - metabolism; Dose-Response Relationship, Drug; Doxorubicin; Doxorubicin - toxicity; Garlic; Glutathione; Glutathione peroxidase; Heart; Heart diseases; Inflammation; Inflammation - chemically induced; Inflammation - prevention & control; Interleukins; Intoxication; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Male; Malondialdehyde; Malondialdehyde - metabolism; Medicine; Medicine & Public Health; Mice; Nitric oxide; Nitric Oxide - metabolism; Oncology; Original Article; Oxidative stress; Oxidative Stress - drug effects; Peroxidase; Pharmacology/Toxicology; Rats; Rodents; Serum levels; Sulfinic Acids - administration & dosage; Sulfinic Acids - pharmacology; Superoxide dismutase; Heart; Oxidative damage; Adriamycin; Inflammation; Garlic; Cardiotoxicity; Antioxidant; Anti-inflammatory; Apoptosis
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-017-3413-7

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.