title: Administration of chromium(III) and manganese(II) as a potential protective approach against daunorubicin-induced cardiotoxicity: in vitro and in vivo experimental evidence.
abstract: Daunorubicin (DNR) is a widely used antitumor drug, but its application is limited because of its cardiotoxic side effects. The present study was designed to investigate the interaction between DNR and cardiac myosin (CM) in the presence of chromium(III) (Cr(3+)) and manganese(II) (Mn(2+)) using fluorescence spectrometry under simulative physiological conditions with the aim of exploring the influence of metal ion on DNR-CM complex and finding out an aggressive approach to abrogate of DNR-induced cardiotoxicity. In detail, the quenching and binding constant of ternary system, including metal ion, DNR, and CM, were measured and compared with the DNR-CM. The data from in vitro experiments indicate that the presence of Cr(3+) or Mn(2+) distinctly decreased the binding force between DNR and CM, and alleviated the cardiac toxicity caused by DNR. In addition, the variations in mice body weight and myocardial enzyme level were examined by in vivo experiments. Animals receiving Cr(3+) or Mn(2+) supplementation of DNR showed preservation of the normal pattern of the heart, especially 2.0 mg Cr(3+)/kg body wt or 50.0 mg Mn(2+)/kg body wt exhibited an obviously protective effect accompanied with body weight raise when compared with the mice treated with DNR alone, decreased the ratio of heart to body weight (BW) and the ratio of left ventricular mass to BW to the normal levels, and inhibited the leak of myocardial enzyme caused by DNR. As a result, this study suggests that pretreatment of lower dose of Cr(3+) (2 mg/kg wt) and moderate dose of Mn(2+) (50 mg/kg wt) might be useful and play an important role in ameliorating the cardiotoxicity of DNR treatment in cancer patients.
authors.affiliation: School of Life Science, Wuchang University of Technology, Wuhan, Hubei Province, 430223, People's Republic of China, znmdly@sina.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Debin
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D054715:Cardiotoxins / Q000009:adverse effects* / Q000494:pharmacology; D002857:Chromium / Q000494:pharmacology*; D003630:Daunorubicin / Q000009:adverse effects* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D054715:Cardiotoxins; D002857:Chromium; D008345:Manganese; D003630:Daunorubicin