Potentiation of doxorubicin cardiotoxicity by iron loading in a rodent model
GS Panjrath, V Patel, CI Valdiviezo, N Narula… - Journal of the American …, 2007 - jacc.org
GS Panjrath, V Patel, CI Valdiviezo, N Narula, J Narula, D Jain
Journal of the American College of Cardiology, 2007•jacc.orgObjectives: The role of iron toward doxorubicin (DOX) cardiotoxicity was studied using a
rodent model of dietary carbonyl iron loading. Background: Doxorubicin, a commonly used
anticancer drug, is known to cause serious and potentially life-threatening cardiotoxicity.
Doxorubicin cardiotoxicity is thought to be mediated through free-radical injury. Methods:
Male Sprague Dawley rats fed iron-rich chow (n= 8) and regular chow (n= 8) were treated
with DOX or saline (4 animals in each arm). Cardiotoxicity was assessed using mortality …
rodent model of dietary carbonyl iron loading. Background: Doxorubicin, a commonly used
anticancer drug, is known to cause serious and potentially life-threatening cardiotoxicity.
Doxorubicin cardiotoxicity is thought to be mediated through free-radical injury. Methods:
Male Sprague Dawley rats fed iron-rich chow (n= 8) and regular chow (n= 8) were treated
with DOX or saline (4 animals in each arm). Cardiotoxicity was assessed using mortality …
Objectives
The role of iron toward doxorubicin (DOX) cardiotoxicity was studied using a rodent model of dietary carbonyl iron loading.
Background
Doxorubicin, a commonly used anticancer drug, is known to cause serious and potentially life-threatening cardiotoxicity. Doxorubicin cardiotoxicity is thought to be mediated through free-radical injury.
Methods
Male Sprague Dawley rats fed iron-rich chow (n = 8) and regular chow (n = 8) were treated with DOX or saline (4 animals in each arm). Cardiotoxicity was assessed using mortality, weight changes, Tc-99m annexin-V imaging, histopathology, and immunohistochemistry.
Results
Animals fed iron-rich chow showed significantly higher DOX cardiotoxicity as evidenced by greater weight loss (107 ± 14 g vs. 55 ± 10 g weight loss, p < 0.05), higher annexin uptake (0.14 ± 0.01% vs. 0.08 ± 0.01% injected dose/g of myocardium, p < 0.05), more severe myocyte injury on electron microscopy, and significantly higher cleaved caspase-3 staining compared with regular chow fed rats given DOX. Feeding iron-rich chow alone did not result in any cardiotoxicity.
Conclusions
Dietary iron loading resulted in a substantially increased DOX cardiotoxicity in rats. Body iron stores as well as its bioavailability in tissue may be important independent predictors of susceptibility to DOX cardiotoxicity in man. Further clinical studies are warranted.
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