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Cardioprotective effects of subcutaneous ebselen against daunorubicin-induced cardiomyopathy in rats.
Basic Clin Pharmacol Toxicol. 2006 Dec; 99(6):412-7.BC

Abstract

Daunorubicin is an anthracycline antitumour agent that can cause severe cardiomyopathy leading to a frequently fatal congestive heart failure. Although the exact molecular mechanisms of cardiotoxicity are not well established, oxidative mechanisms involving daunorubicin-induced superoxide anion production have been proposed. In the present study, we showed that ebselen a seleno-organic compound exhibiting glutathione peroxidase-like and antioxidant activities, significantly ameliorated daunorubicin-induced cardiomyopathy. Subcutaneous administration of ebselen to daunorubicin-treated rats showed significant improvement in serum cardiac indices including creatine kinase isoenzyme and lactate dehydrogenase as well as serum glutathione (GSH) peroxidase. Moreover, myocardium of daunorubicin/ebselen-treated rats showed significant improvement in daunorubicin-induced depletion of GSH peroxidase activity and reduced glutathione content, in addition to attenuation of daunorubicin-induced increase in cardiac malondialdehyde production and total nitrate/nitrite concentration levels. These results were confirmed by histopathological examination of ventricles of daunorubicin/ebselen-treated rats that revealed significant improvement of the characteristic cardiomyopathic changes induced by daunorubicin treatment. Interestingly, control rats treated with ebselen showed significant elevation in serum lactate dehydrogenase activity, cardiac malondialdehyde production and total nitrate/nitrite concentration levels compared with the untreated control animals. In conclusion, ebselen treatment significantly alleviates daunorubicin-induced cardiomyopathy.

Authors+Show Affiliations

Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. sherifibrahem@yahoo.co.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17169121

Citation

Saad, Sherif Y., et al. "Cardioprotective Effects of Subcutaneous Ebselen Against Daunorubicin-induced Cardiomyopathy in Rats." Basic & Clinical Pharmacology & Toxicology, vol. 99, no. 6, 2006, pp. 412-7.
Saad SY, Najjar TA, Arafah MM. Cardioprotective effects of subcutaneous ebselen against daunorubicin-induced cardiomyopathy in rats. Basic Clin Pharmacol Toxicol. 2006;99(6):412-7.
Saad, S. Y., Najjar, T. A., & Arafah, M. M. (2006). Cardioprotective effects of subcutaneous ebselen against daunorubicin-induced cardiomyopathy in rats. Basic & Clinical Pharmacology & Toxicology, 99(6), 412-7.
Saad SY, Najjar TA, Arafah MM. Cardioprotective Effects of Subcutaneous Ebselen Against Daunorubicin-induced Cardiomyopathy in Rats. Basic Clin Pharmacol Toxicol. 2006;99(6):412-7. PubMed PMID: 17169121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardioprotective effects of subcutaneous ebselen against daunorubicin-induced cardiomyopathy in rats. AU - Saad,Sherif Y, AU - Najjar,Tawfeeg A, AU - Arafah,Maha M, PY - 2006/12/16/pubmed PY - 2007/2/3/medline PY - 2006/12/16/entrez SP - 412 EP - 7 JF - Basic & clinical pharmacology & toxicology JO - Basic Clin. Pharmacol. Toxicol. VL - 99 IS - 6 N2 - Daunorubicin is an anthracycline antitumour agent that can cause severe cardiomyopathy leading to a frequently fatal congestive heart failure. Although the exact molecular mechanisms of cardiotoxicity are not well established, oxidative mechanisms involving daunorubicin-induced superoxide anion production have been proposed. In the present study, we showed that ebselen a seleno-organic compound exhibiting glutathione peroxidase-like and antioxidant activities, significantly ameliorated daunorubicin-induced cardiomyopathy. Subcutaneous administration of ebselen to daunorubicin-treated rats showed significant improvement in serum cardiac indices including creatine kinase isoenzyme and lactate dehydrogenase as well as serum glutathione (GSH) peroxidase. Moreover, myocardium of daunorubicin/ebselen-treated rats showed significant improvement in daunorubicin-induced depletion of GSH peroxidase activity and reduced glutathione content, in addition to attenuation of daunorubicin-induced increase in cardiac malondialdehyde production and total nitrate/nitrite concentration levels. These results were confirmed by histopathological examination of ventricles of daunorubicin/ebselen-treated rats that revealed significant improvement of the characteristic cardiomyopathic changes induced by daunorubicin treatment. Interestingly, control rats treated with ebselen showed significant elevation in serum lactate dehydrogenase activity, cardiac malondialdehyde production and total nitrate/nitrite concentration levels compared with the untreated control animals. In conclusion, ebselen treatment significantly alleviates daunorubicin-induced cardiomyopathy. SN - 1742-7835 UR - https://www.unboundmedicine.com/medline/citation/17169121/Cardioprotective_effects_of_subcutaneous_ebselen_against_daunorubicin_induced_cardiomyopathy_in_rats_ L2 - https://doi.org/10.1111/j.1742-7843.2006.pto_523.x DB - PRIME DP - Unbound Medicine ER -