Doxorubicin, widely used chemotherapy drug for ovarian, bladder, lung, thyroid and stomach cancers, has the potential to cause heart toxicity that can lead to congestive heart failure, a study has found.
University of Alabama at Birmingham researchers, led by assistant professor Ganesh Halade, used a mouse model to study the effect of doxorubicin on immunometabolism - the study of how metabolism regulates immune cell function.
In the study, conducted on mice, doxorubicin induced fibrosis in the heart, increased the programmed cell death called apoptosis and impaired the pumping of the heart. The drug also caused a wasting syndrome in the heart and the spleen.
The UAB researchers found that doxorubicin induced irreversible dysregulation that lowered the levels of enzymes in the left ventricle of the heart, which in turn reduced the levels of bioactive lipids mediators produced by these enzymes, mediators that usually would help resolve inflammation.
In the spleen, doxorubicin also poisoned a special group of marginal zone immune cells called CD169+ macrophages, causing the spleen to shrink in size.
Doxorubicin also caused an imbalance of the cell-signalling molecules called chemokines and cytokines, and this imbalance suggested suppressed defence capacity of spleen-leukocyte immune cells.
The UAB researchers specifically found decreased levels of tumour necrosis factor-alpha in the spleen, and decreased levels of the immune-cells reparative marker MRC-1, also known as CD206, in the heart.
Thus, Halade said, "Doxorubicin appears to have a splenocardiac impact in this non-cancer model."
