A chemotherapy drug, widely used for treatment of ovarian, bladder, lung, thyroid and stomach cancers, has the potential to cause heart toxicity that can lead to congestive heart failure, a study led by a professor of Indian origin, has found.

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 study, led by Ganesh Halade, Assistant Professor at the University of Alabama in the US, found that disruption of the metabolism that controls immune responses in the spleen and heart is vital for heart maintenance, repair and control of inflammation.

For the study, published in the American Journal of Physiology -- Heart and Circulatory Physiology, the team used a mouse model to study the effect of doxorubicin on immunometabolism -- the study of how metabolism regulates immune cell function. A dysregulated immunometabolism impairs resolution of inflammation, and chronic, non-resolving inflammation can lead to advanced heart failure. Halade's team found that doxorubicin is also involved in the deleterious response to the spleen.

First, doxorubicin was shown to induce 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 diminish in size. It 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.

Specifically, the researchers 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, doxorubicin appears to have a splenocardiac impact in this non-cancer model, Halade said.