Tags

Type your tag names separated by a space and hit enter

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.

    ,

    Department of Pharmacology & Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

    ,

    Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.

    ,

    Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.

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

    Source

    European journal of pharmacology 728: 2014 Apr 05 pg 107-18

    MeSH

    Animals
    Anti-Inflammatory Agents, Non-Steroidal
    Antibiotics, Antineoplastic
    Antioxidants
    Apoptosis
    Biomarkers
    Cardiomyopathies
    Doxorubicin
    Electrocardiography
    Flavonoids
    Immunohistochemistry
    Male
    Nitric Oxide
    Oxidative Stress
    Rats
    Tumor Necrosis Factor-alpha

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    24509133

    Citation

    Mantawy, Eman M., et al. "Chrysin Alleviates Acute Doxorubicin Cardiotoxicity in Rats Via Suppression of Oxidative Stress, Inflammation and Apoptosis." European Journal of Pharmacology, vol. 728, 2014, pp. 107-18.
    Mantawy EM, El-Bakly WM, Esmat A, et al. Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Eur J Pharmacol. 2014;728:107-18.
    Mantawy, E. M., El-Bakly, W. M., Esmat, A., Badr, A. M., & El-Demerdash, E. (2014). Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. European Journal of Pharmacology, 728, pp. 107-18. doi:10.1016/j.ejphar.2014.01.065.
    Mantawy EM, et al. Chrysin Alleviates Acute Doxorubicin Cardiotoxicity in Rats Via Suppression of Oxidative Stress, Inflammation and Apoptosis. Eur J Pharmacol. 2014 Apr 5;728:107-18. PubMed PMID: 24509133.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. AU - Mantawy,Eman M, AU - El-Bakly,Wesam M, AU - Esmat,Ahmed, AU - Badr,Amira M, AU - El-Demerdash,Ebtehal, Y1 - 2014/02/06/ PY - 2013/10/21/received PY - 2014/01/25/revised PY - 2014/01/29/accepted PY - 2014/2/11/entrez PY - 2014/2/11/pubmed PY - 2015/3/3/medline KW - Apoptosis KW - Cardiotoxicity KW - Chrysin KW - Doxorubicin KW - Inflammation KW - Oxidative stress SP - 107 EP - 18 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 728 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/24509133/Chrysin_alleviates_acute_doxorubicin_cardiotoxicity_in_rats_via_suppression_of_oxidative_stress_inflammation_and_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(14)00101-0 DB - PRIME DP - Unbound Medicine ER -