Study Links Free Radicals to Cancer Heart Damage

In fruit flies, antioxidants reverse tumor-related heart dysfunction.

A new study in animal models shows that the presence of a cancerous tumor alone can lead to heart damage and suggests that the culprits are molecules called free radicals that interact with specific cells in the heart.

Tumors in mice and fruit flies have caused varying degrees of cardiac dysfunction, particularly a decrease in the heart’s blood-pumping abilities.

Adding specific types of antioxidants to foods eaten by fruit flies with tumors reversed the damage to their hearts – a finding suggesting free radical damage was the likely link between cancer and dysfunction cardiac.

“Cancer becomes a systemic disease. It’s not just a tumor that does one thing, ”said co-lead author Shubha Gururaja Rao, assistant professor of pharmacology at Ohio Northern University and assistant faculty member in physiology and cell biology at Ohio. State University.

Most of what is known about the link between cancer and heart damage relates to the toxic effects of chemotherapy and the muscle atrophy commonly experienced by cancer patients.

This is the first study to use a genetic model to investigate the direct effect of cancer on heart dysfunction. Researchers have found that different genes associated with cancer affect the heart in different ways – a sign that genetic information may one day guide heart protection treatment decisions in cancer patients.

“This suggests that treatment might be suitable if you know which genes cause cancer or are abnormal in certain cancers,” said Harpreet Singh, co-lead author of the study and associate professor of physiology and biology. cell phone at Ohio State.

“Above all, we want to make clinicians aware that when cancer is first detected, long before muscle wasting sets in or chemotherapy begins, other organs get the message and are affected. “

The study is published in the journal Antioxidants.

It is estimated that 50 to 80% of cancer patients develop a muscle atrophy called cachexia, which can lead to heart failure, and radiation and chemotherapy treatments are associated with toxicity-related damage to the heart muscle.

However, new research suggests that heart problems can appear before cancer treatment or muscle wasting. The Ohio State team noted that a study recently published in the Journal of the America Heart Association have reported detection of abnormalities in heart tissue and heart function in human cancer patients before cancer treatment is initiated.

In this new study, Ohio State researchers injected breast cancer cells into the mammary glands of mice and measured the animals’ heart function four weeks later. They found that two measures of cardiac pumping rate, left ventricular ejection fraction and fractional shortening, decreased by approximately 20% and 22%, respectively.

In fruit flies, the team overexpressed carcinogenic genes to trigger tumor development in the eyes of flies. Scientists observed a significantly lower ejection fraction and fractional shortening – similar to what was seen in mice with tumors – as well as an increased heart rate in flies with tumors.

The researchers found an increased rate of total body production as well as a higher total number of free radicals – also known as reactive oxygen species – in fruit flies with tumors compared to witnesses. The rate of production of reactive oxygen species was also significantly higher in mice with tumors compared to controls.

To test whether the supplements could reverse tumor-related heart damage, four antioxidants were added to the fruit fly food for seven days: glutathione (GSH), vitamin E, CoQ10 or vitamin C.

The results showed that everything except vitamin C restored flies’ heart function to normal levels.

“We don’t yet know why one antioxidant works over another,” Rao said, adding that because the flies ate the antioxidants in their food, the researchers also don’t have definitive information on the doses of the antioxidants. antioxidants at this stage.

She and Singh also pointed out that reactive oxygen species is only one identified mechanism of tumor-related heart damage, and that much remains to be learned about how antioxidants might fit into a diet. treatment.

Although this research focused on a carcinogenic gene to study the mechanism of heart damage in fruit flies, the researchers first tested the effects of several carcinogenic genes in flies. The affected heart function and the intensity of the effects on the heart varied depending on the gene. Rao plans to continue genetic studies in fruit flies and test the restorative effects of antioxidants on the hearts of mice with tumors.

Singh is working with clinicians at Ohio State and other institutions to collect blood samples from cancer patients with heart failure.

“The signal travels from the tumor to the heart, and the tissue connecting these sites is the blood – so the question is whether reactive oxygen species are traveling in the blood? he said. “Clinically, our priority is to research the correlation between the different oncogenic pathways and heart failure. Second, we want to see what the message is and if we can prescribe antioxidants. “

Reference: “Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS” by Priyanka Karekar, Haley N. Jensen, Kathryn LG Russart, Devasena Ponnalagu, Sarah Seeley, Shridhar Sanghvi, Sakima A. Smith, Leah M. Pyter, Harpreet Singh and Shubha Gururaja Rao, August 18, 2021, Antioxidants.
DOI: 10.3390 / antiox10081299

Additional co-authors include Priyanka Karekar, Haley Jensen, Kathryn Russart, Devasena Ponnalagu, Shridhar Sanghvi, Sakima Smith and Leah Pyter from Ohio State and Sarah Seeley from Ohio Northern University (UN).

The work was supported by grants from the Commonwealth Universal Research Enhancement Program, the WW Smith Charitable Trust, the American Heart Association, the National Institutes of Health, the Davis Heart and Lung Research Institute in Ohio, and start-up funds from the UN.