Aqueous fish extract increases survival in the mouse model of cytostatic toxicity.
BACKGROUND
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.


METHODS
A LMW fraction (<500 Da) of the aqueous phase of cod light muscle (AOX) was used for treatment of male BALB/c mice (approximately 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.


RESULTS
Mortality 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.


CONCLUSIONS
The 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.
Omerovic
Elmir
E
Wallenberg Laboratory at Sahlgrenska Academy, Göteborg University Göteborg, Sweden. elmir@wlab.gu.se
Linbom
Malin
M
Råmunddal
Truls
T
Lindgård
Ann
A
Undeland
Ingrid
I
Sandberg
Ann-Sofie
AS
Soussi
Bassam
B
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D000970:Antineoplastic Agents / Q000032:analysis / Q000494:pharmacology; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D004452:Echocardiography; D048389:Gadus morhua; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000737:chemistry; D011685:Purine Nucleotides / Q000378:metabolism; D014020:Tissue Extracts / Q000032:analysis / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000975:Antioxidants; D011685:Purine Nucleotides; D014020:Tissue Extracts; D004317:Doxorubicin