Potentiation of Doxorubicin Cardiotoxicity by Iron Loading in a Rodent Model
Gurusher S. Panjrath, MD*,
Virender Patel, MD*,
Carolina I. Valdiviezo, MD ,
Navneet Narula, MD ,
Jagat Narula, MD, PhD, FACC* and
Diwakar Jain, MD, FACC*,*
* Division of Cardiology, Drexel University College of Medicine, Philadelphia, Pennsylvania
Pathology Department, University of Pennsylvania, Philadelphia, Pennsylvania
Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, New York.
View larger version (15K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2 Weight Change
Both iron-rich chow and regular chow fed control animals gained weight. Regular chow fed animals treated with doxorubicin (DOX) showed a progressive weight loss. Weight loss in iron-rich chow group treated with DOX was significantly higher compared with that in other groups.
|
|
View larger version (84K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3 99mTc Annexin-V Imaging
Planar whole body (top) and ex-vivo images of heart (bottom) of animals from each subgroup on 99mTc annexin-V imaging. There is intense Annexin uptake in liver (L) and spleen (S) with variable uptake in the heart (arrows). No myocardial uptake seen in control group (A and B). Regular chow and iron-rich chow fed animals treated with doxorubicin (DOX) show intense cardiac uptake (C and D).
|
|
View larger version (34K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5 Myocardial Iron
A mild increase in myocardial iron content is seen in iron-rich chow fed animals in both control and doxorubicin (DOX)-treated groups. *p < 0.05 compared with DOX and saline.
|
|
View larger version (141K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6 Light Microscopy
Light microscopy of hematoxylin- and eosin-stained myocardial tissue shows no signs of myocyte injury in (A) regular chow fed animals treated with saline, (B) iron-rich chow fed animals treated with saline, (C) regular chow fed animals treated with DOX, and (D) iron-rich chow fed animals treated with doxorubicin (DOX).
|
|
View larger version (117K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 7 Electron Microscopy
(A) No loss of myofilaments is seen in regular chow fed saline-treated animal. (B) Minimal myofilament loss in iron-rich chow fed animal treated with saline. (C) Regular chow fed doxorubicin-treated animal showed infrequent areas of myofilament loss (arrow) without any sarcoplasmic swelling. (D) Larger areas of myofilament loss (arrow) seen in iron-rich chow fed animals treated with doxorubicin. Iron-rich chow fed animals treated with doxorubicin show frequent and large areas of myofilament loss (arrow) accompanied by swelling of sarcoplasmic reticulum, which are characteristic changes seen in doxorubicin cardiotoxicity. N = nucleus.
|
|
View larger version (146K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 8 Activated Caspase-3 Immunohistochemistry of Myocardial Specimens
Activated caspase-3 was present in the cytoplasm of cells with morphology consistent with apoptosis. Positive staining is seen in myocardium of animals treated with doxorubicin (C and D). No staining is seen in control animals fed (A) regular chow or (B) iron-rich chow. Iron-rich chow fed animals treated with doxorubicin (D) show a greater area of staining involving higher number of myocytes compared with regular chow fed animals treated with doxorubicin (C).
|
|
|
