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Eur J Pharmacol. 2014 Apr 5;728:107-18. doi: 10.1016/j.ejphar.2014.01.065. Epub 2014 Feb 6.

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

Author information

1
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.
2
Department of Pharmacology & Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
3
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt. Electronic address: ebtehal_dm@yahoo.com.

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.

KEYWORDS:

Apoptosis; Cardiotoxicity; Chrysin; Doxorubicin; Inflammation; Oxidative stress

PMID:
24509133
DOI:
10.1016/j.ejphar.2014.01.065
[Indexed for MEDLINE]

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