One of the biggest issues with chemotherapy treatments is their inherent toxicities. Most chemotherapy drugs are toxic to all cells but happen to accumulate in cancer cells for one reason or another. Preventing this toxicity is an area of keen interest in the future of cancer therapies.
Doxorubicin is a chemotherapeutic drug that attacks the DNA of cancer cells. Unfortunately, it often has off-target cardiotoxicity. Studies point to the source of the cardiotoxicity is oxidative stress, which can induce programmed cell death in cells. A new study out of Nazarbayaev University in Kazakhstan hypothesized that if you could prevent the oxidative stress, you might be able to avert doxorubicin’s cardiotoxic side effects.
The study would focus on the use of polyphenol compounds and how they affected doxorubicin treated mice. Polyphenols are antioxidants, capable of neutralizing the harmful free radicals generated by oxidative stress. The team considered several candidates, but settled on grape polyphenol extract and gave it to mice alongside doxorubicin to test if any could alleviate doxorubicin’s cardiotoxicity.
The team first wanted to confirm doxorubicin’s cardiotoxicity on the mice. When doxorubicin was administered alone, there was a spike in oxidative stress and cardiomyocyte damage markers. This observation was seen in several other studies, confirming doxorubicin’s cardiotoxicity in their model.
Next, they examined if treatment with grape polyphenol extract could change doxorubicin’s toxicity. The most apparent effect they saw was in the blood, where there was a pronounced decrease in oxidative stress markers. This didn’t translate into heart damage biomarkers; however, there was no indication that polyphenol treatment prevented heart damage.
Looking at heart cells under an electron microscope, doxorubicin caused abnormalities to many cellular structures. Polyphenol treatment reversed much of this damage, except in the mitochondrion. Mitochondria are the centers of oxidant production and antioxidant machinery in the cell and retained the irregular structure caused by doxorubicin even after polyphenol treatment. This suggested the cardiotoxicity could not be entirely reversed with polyphenol treatment alone.
This study showed the treatment with grape polyphenol extract could reduce the cardiotoxic effects of doxorubicin. The polyphenols could not prevent cardiac damage as measured by biomarkers but could reduce oxidative stress in the blood and reduce the damage done to cardiac cells. Polyphenols are common in things like tea, berries, and wines and have been suggested to have anti-cancer effects. This study supports their possible use as therapeutics, though more research is needed to achieve the most effective treatment.
The study concludes, “In conclusion, the results of the current study showed that grape polyphenol concentrate, has the ability to reduce ROS production, improve antioxidant enzyme activities, and mitigates myocardial cell damage.”
Sources: Nature Scientific Reports, Case Western University
