title: 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: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.
authors: Eman M
authors: EM
authors: Mantawy
authors: Department of Pharmacology & Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors: Wesam M
authors: WM
authors: El-Bakly
authors: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.
authors: Ahmed
authors: A
authors: Esmat
authors: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.
authors: Amira M
authors: AM
authors: Badr
authors: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt. Electronic address: ebtehal_dm@yahoo.com.
authors: Ebtehal
authors: E
authors: El-Demerdash
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000032:analysis; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004317:Doxorubicin / Q000009:adverse effects*; D004562:Electrocardiography; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D015415:Biomarkers; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C043561:chrysin; D004317:Doxorubicin
keywords: Apoptosis; Cardiotoxicity; Chrysin; Doxorubicin; Inflammation; Oxidative stress