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Efficacy of melatonin, mercaptoethylguanidine and 1400W in doxorubicin‐ and trastuzumab‐induced cardiotoxicity
Author(s) -
Ozturk Mustafa,
Ozler Mehmet,
Kurt Yasemin Gulcan,
Ozturk Bekir,
Uysal Bulent,
Ersoz Nail,
Yasar Mehmet,
Demirbas Seref,
Kurt Bulent,
Acikel Cengizhan,
Oztas Yesim,
Arpaci Fikret,
Topal Turgut,
Ozet Ahmet,
Ataergin Selmin,
Kuzhan Okan,
Oter Sukru,
Korkmaz Ahmet
Publication year - 2011
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2010.00818.x
Subject(s) - cardiotoxicity , melatonin , trastuzumab , doxorubicin , medicine , chemotherapy , oncology , cancer , breast cancer
Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N ‐(3‐(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague‐Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px), as well as serum levels of creatine phosphokinase (CK‐MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH‐Px activities were significantly reduced in rats with DOX‐ or DOX+TRAST‐induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK‐MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX‐ and DOX+TRAST‐treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400W are effective in preventing DOX‐ or DOX+TRAST‐induced cardiotoxicity.