Maintenance of myocardial levels of vitamin A in heart failure due to adriamycin.
The therapeutic use of adriamycin (doxorubicin), a potent antitumor antibiotic, is limited by the development of dose-dependent cardiomyopathy. Increased oxidative stress due to adriamycin is considered to play a role in the pathogenesis of this toxic effect. In this study, we examined the levels and redistribution of vitamin A (a potent non-enzymatic antioxidant) in adriamycin-induced cardiomyopathy in rats. Three weeks after the adriamycin (ADR) treatment, animals were hemodynamically assessed and different tissues were analyzed for total retinol (vitamin A), (3)H-radio-labeled retinol, retinol palmitate and vitamin E. At 3 weeks, animals in the ADR group were hemodynamically and clinically confirmed to be in heart failure. In the ADR group, total retinol levels in heart and plasma were unchanged. However, levels of the (3)H radio-labeled fraction of retinol were significantly increased in both organs suggesting increased turnover. In the liver, the levels of total retinol and retinol palmitate were significantly decreased, while the radio-labeled fraction of retinol was significantly increased suggesting mobilization of retinol from this organ. Alpha tocopherol (vitamin E) levels were found unchanged in hearts of the ADR animals, while its levels in the plasma and liver were significantly increased. Increased radio-labeled fraction, without any change in the total retinol in the heart, suggested that vitamin A is utilized more by the heart under increased oxidative stress due to adriamycin. Its levels in the plasma and the heart may have been maintained at the expense of the loss from the liver.
Danelisen
Igor
I
Institute of Cardiovascular Science, St. Boniface General Hospital Research Center, Department of Physiology, University of Manitoba, Manitoba, R2H 2A6, Canada.
Palace
Vince
V
Lou
Huiquan
H
Singal
Pawan K
PK
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects*; D006333:Heart Failure / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D009929:Organ Size; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014801:Vitamin A / Q000097:blood / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000097:blood
D000970:Antineoplastic Agents; D014801:Vitamin A; D004317:Doxorubicin; D024502:alpha-Tocopherol