SEP 22, 2020 1:15 PM PDT

Investigating the Mechanism Behind 5-Fluorouracil's Cardiotoxicity

WRITTEN BY: Jasper Cantrell

Cancer therapies have come quite far, with several options available for many cancers. An issue that has plagued many of these treatments is toxicity, with cardiotoxicity being one of the biggest problems.

The chemotherapeutic 5-fluorouracil is an example of a chemotherapy that can cause severe cardiotoxicity. Symptoms from the toxicity vary wildly from heart failure to hypertension. The mechanisms behind these symptoms are still not fully understood, with many studies pointing to different explanations. A new study out of Cairo University sought to investigate further and possibly find the root cause.

The study intended to look at the mechanisms surrounding 5-fluorouracil’s toxicity to isolate what could be happening. They examined several different cellular pathways tied to cardiovascular disease and sought to investigate if the biomarkers brain natriuretic peptide (BNP) and NT-proBNP might act as prognosis indicators. Finally, they wanted to see if the drug simvastatin could protect the heart from 5-fluorouracil’s cardiotoxicity.

To do this, the study relied on mouse models. Mice were split into four groups; one treated with 5-fluorouracil alone, one treated with simvastatin alone, one treated with both, and a control to compare them. Biomarkers and clinical indicators were taken from each group and compared against each other.

The group treated with 5-fluorouracil alone saw a dramatic decline in survival. Simvastatin seemed to alleviate most of the problems, with the mice having a milder mortality rate. 5-fluorouracil also appeared to induce several adverse cardiac events, which simvastatin coadministration again seemed to prevent.

Following several biomarkers, they found that while some universal cardiac biomarkers were silent to 5-fluorouracil cardiotoxicity, NT-proBNP was not. 5-fluorouracil increased NT-proBNP three-fold, which simvastatin managed to bring down significantly. 5-fluorouracil also seemed to activate the ERK1/2 and ROCK pathways and increase oxidative stress and inflammation. Simvastatin again managed to alleviate most of these symptoms, although not wholly preventing them.

This study identified an interconnected set of several pathways, including oxidative stress and inflammation, that could help explain the mechanism behind 5-fluorouracil’s cardiotoxicity. It also identifies NT-proBNP as a better prognostic marker for cardiotoxicity in this case. Simvastatin seemed to have a strong cardioprotective effect against 5-fluorouracil, although this study did not test it in actual cancer treatment.

The study concludes, “The current study highlights the involvement and crosstalk of several signaling pathways in the 5-FU-induced cardiac injury.” and “The study also substantiates the cardioprotective potential of Sim against 5-FU-induced injury by manipulating these pathways.”

About the Author
  • Hey everyone! My name is Jasper and, considering I am pretty new here to Labroots, I figured I would introduce myself. I received my bachelor’s from the University of California at Riverside back in 2016. I started off my career a few years ago with a job at a University over in New York, before moving over into the industry. I'm happy to be writing content for Labroots, and I hope you enjoy it!
You May Also Like
AUG 05, 2020
Cannabis Sciences
Cannabis Might Trigger Heart Problems Says AHA
AUG 05, 2020
Cannabis Might Trigger Heart Problems Says AHA
The American Heart Association (AHA) has produced a new statement about medical marijuana and recreational cannabis. The ...
AUG 10, 2020
Cardiology
Can Statins be Used to Treat Strokes?
AUG 10, 2020
Can Statins be Used to Treat Strokes?
When a blood clot forms in an artery that supplies the brain with oxygen, obstructing it, a stroke can occur. Strokes ca ...
AUG 11, 2020
Cardiology
Investigating the Link Between a Kidney Protein and Hypertension
AUG 11, 2020
Investigating the Link Between a Kidney Protein and Hypertension
Hypertension, or high blood pressure, is a common cardiovascular condition with plenty of treatment options and preventi ...
AUG 20, 2020
Cardiology
Cilia are Found to Have Vesicles That May Influence Heart Disease
AUG 20, 2020
Cilia are Found to Have Vesicles That May Influence Heart Disease
Cells have many specialized organelles, including a kind of signaling hub called a cilium, which sticks out of the surfa ...
AUG 30, 2020
Cardiology
Plant-Based Diets Are Healthier When Low in Processed Foods
AUG 30, 2020
Plant-Based Diets Are Healthier When Low in Processed Foods
While many research studies have shown that reducing meat intake and eating more plant-based foods is healthier, not all ...
SEP 11, 2020
Health & Medicine
Trans Fat Regulations Protect Three Billion People Worldwide
SEP 11, 2020
Trans Fat Regulations Protect Three Billion People Worldwide
The World Health Organization (WHO) recently released a progress report on its five-year initiative for the global elimi ...
Loading Comments...