Dietary fish oil does not prevent doxorubicin-induced cardiomyopathy in rats.
BACKGROUND
Dietary fish oil potentiates the susceptibility of cellular membranes to lipid peroxidation, although it is also known to have beneficial effects on the development of cardiovascular diseases.


OBJECTIVE
The effects of dietary fish oil against doxorubicin-induced cardiomyopathy, in which free radicals and lipid peroxidation are involved, were investigated in rats.


METHODS
Sprague-Dawley rats (100 g) were fed a standard diet or a high fish oil diet (containing 10% fish oil) throughout the experimental period. Four weeks after starting each diet, experimental rats were treated with doxorubicin (cumulative dose 15 mg/kg) or vehicle (0.28 M dextrose solution). After three weeks of doxorubicin treatment, the cardiac performance, myocardial lipid peroxidation and myocardial vitamin E level were assessed.


RESULTS
Compared with control rats, doxorubicin-treated rats showed a significantly increased mortality rate (P<0.05), and significantly decreased systolic blood pressure and left ventricular fractional shortening (P<0.01). The myocardial thiobarbituric acid-reactive substance level was significantly higher in doxorubicin-treated rats than in control rats (P<0.01), while the myocardial vitamin E level was significantly lower (P<0.05). Dietary fish oil enhanced the myocardial lipid peroxidation caused by doxorubicin, which was associated with a further decrease in myocardial vitamin E level. As a result, the rats treated with both doxorubicin and the high fish oil diet showed the highest mortality rate and the lowest cardiac performance of all the experimental groups.


CONCLUSIONS
Dietary fish oil may reduce antioxidant defences and accelerate susceptibility of the myocardium to lipid peroxidation in rats under doxorubicin treatment. This may partly explain why dietary fish oil does not prevent doxorubicin-induced cardiomyopathy.
Matsui
Hideo
H
Internal Medicine II, Nagoya University School of Medicine, Nagoya, Japan. hideom@med.nagoya-u.ac.jp
Morishima
Itsuro
I
Hayashi
Kazunori
K
Kamiya
Hiroki
H
Saburi
Yoshihiro
Y
Okumura
Kenji
K
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D009202:Cardiomyopathies / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005395:Fish Oils / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008955:Models, Cardiovascular; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D014810:Vitamin E / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D004042:Dietary Fats, Unsaturated; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D014810:Vitamin E; D004317:Doxorubicin