Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis.

Abstract

Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs; however, its incidence of cardiotoxicity compromises its therapeutic index. Chrysin, a natural flavone, possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer. The present study was designed to investigate whether chrysin could protect against DOX-induced acute cardiotoxicity; and if so, unravel the molecular mechanisms of this protective effect. Chrysin was administered to male albino rats once daily for 12 consecutive days at doses of 25 and 50mg/kg orally. DOX (15 mg/kg; i.p.) was administered on day 12. Chrysin pretreatment significantly protected against DOX-induced myocardial damage which was characterized by conduction abnormalities, increased serum creatine kinase isoenzyme-MB (CK-MB), and lactate dehydrogenase (LDH) and myofibrillar disarrangement. As indicators of oxidative stress, DOX caused significant glutathione depletion, lipid peroxidation and reduction in activities of antioxidant enzymes; catalase (CAT) and superoxide dismutase (SOD). Chrysin pretreatment significantly attenuated DOX-induced oxidative injury. Additionally, DOX provoked inflammatory responses by increasing the expressions of nuclear factor kappa-B (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the levels of tumor necrosis factor-alpha (TNF-α) and nitric oxide while chrysin pretreatment significantly inhibited these inflammatory responses. Furthermore, DOX induced apoptotic tissue damage by increasing Bax and cytochrome c expressions and caspase-3 activity while decreasing the expression of Bcl-2. Chrysin pretreatment significantly ameliorated these apoptotic actions of DOX. Collectively, these findings indicate that chrysin possesses a potent protective effect against DOX-induced acute cardiotoxicity via suppressing oxidative stress, inflammation and apoptotic tissue damage.

• Authors: Eman M Mantawy, Wesam M El-Bakly, Ahmed Esmat, Amira M Badr, Ebtehal El-Demerdash
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 728 Pg. 107-18 (Apr 05 2014) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 24509133 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antibiotics, Antineoplastic
• Antioxidants
• Biomarkers
• Flavonoids
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• chrysin
• Doxorubicin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, metabolism, therapeutic use)
• Antibiotics, Antineoplastic (adverse effects)
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Biomarkers (analysis)
• Cardiomyopathies (chemically induced, metabolism, pathology, prevention & control)
• Doxorubicin (adverse effects)
• Electrocardiography
• Flavonoids (administration & dosage, therapeutic use)
• Immunohistochemistry
• Male
• Nitric Oxide (immunology, metabolism)
• Oxidative Stress (drug effects)
• Rats
• Tumor Necrosis Factor-alpha (immunology, metabolism)