Abstract

BackgroundTreatment of cancer patients with anthracycline antibiotic doxorubicin (DOX) may be complicated by development of acute and chronic congestive heart failure (CHF), malignant arrhythmias and death. The aim of this study was to test whether an aqueous low molecular weight (LMW) extract from cod muscle decreases acute mortality in the mouse model of acute CHF caused by DOX.MethodsA LMW fraction (<500 Da) of the aqueous phase of cod light muscle (AOX) was used for treatment of male BALB/c mice (~25 g, n = 70). The animals were divided into four groups, DOX + AOX (n = 20), DOX + saline (NaCl) (n = 30), NaCl + AOX (n = 10) and NaCl only (n = 10). Echocardiography was performed in the separate subgroups (DOX treated n = 6 and controls n = 6) to verify the presence and the grade of acute CHF. The cod extract was delivered by subcutaneously implanted osmotic minipumps over the period of 2 weeks. High-dose injection of DOX was administered to randomly selected animals. The animals received single intraperitoneal injection of DOX (25 mg/kg) and were followed over two weeks for mortality.ResultsMortality rate was 68% lower (p < 0.05) in the mice treated with the extract. The analyses of cod extract have shown strong antioxidative effect in vitro.ConclusionThe aqueous LMW cod muscles extract decreases mortality in the mouse model of DOX induced acute CHF. This effect may be mediated by cardioprotection through antioxidative mechanisms.

Highlights

  • The anthracycline antibiotic doxorubicin (DOX) is one of the most effective antitumor agents against human malignancies such as leukemia, lymphomas and many solid tumors [1,2,3]

  • The most prominent gross pathologic change in the mice treated with DOX was excessive amounts of pericardial, pleural and peritoneal fluid indicating the presence of systemic as well as local toxic effect

  • On a gross pathological cardiac examination the hearts of the DOX treated animals were enlarged and there were signs of pericarditis with multiple adhesions of connective tissue formed between the pericardium and the inner thoracic wall

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Summary

Introduction

The anthracycline antibiotic doxorubicin (DOX) is one of the most effective antitumor agents against human malignancies such as leukemia, lymphomas and many solid tumors [1,2,3]. The treatment of cancer patients with DOX may be complicated by deleterious side effects. Journal of Experimental & Clinical Cancer Research 2008, 27:81 http://www.jeccr.com/content/27/1/81 acute and chronic congestive heart failure (CHF), malignant arrhythmias and death [4,5]. Many different cardioprotective agents have been tested for prevention of DOX toxicity experimentally and clinically but with limited success[6]. We hypothesize that aqueous fish muscle extract may improve survival in mouse model of acute heart failure. Treatment of cancer patients with anthracycline antibiotic doxorubicin (DOX) may be complicated by development of acute and chronic congestive heart failure (CHF), malignant arrhythmias and death. The aim of this study was to test whether an aqueous low molecular weight (LMW) extract from cod muscle decreases acute mortality in the mouse model of acute CHF caused by DOX

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