Key Points
- Gold particles coated with apigenin, an NAD+-boosting compound, protected rats from heart damage caused by an effective cancer drug (doxorubicin).
- These gold particles substantially reduced body and heart weight loss in rats treated with doxorubicin.
- Injury indicators were reduced dramatically by treatment with apigenin-coated gold particles.
Tiny bits of gold covered with a chemical found in a range of plants, including chamomile, might protect the heart from damage caused by an effective drug for cancer. Gold nanoparticles covered with apigenin—which has several modes of action, including boosting the levels of the indispensable molecule NAD+—prevented heart cell death and the loss of functional heart cells in rats treated with the anti-cancer therapeutic doxorubicin.
Doxorubicin Causes Severe Heart Toxicity
The drug doxorubicin is used to treat both hematological and solid malignant tumors in adults and children. But its use in clinical settings has been linked to harmful effects on the heart (cardiotoxicity) and other parts of the body, making it unsuitable for long-term use. Multiple studies show that doxorubicin causes cardiotoxicity and cardiomyopathy—a disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body and can cause heart failure—through numerous pathways, including the death of the key contractile cells of the heart (cardiomyocytes). Therefore, inhibiting programmed cell death (apoptosis) may help ward off doxorubicin’s cardiotoxic effects.
Apigenin-coated Gold Nanoparticles Protect Against Doxorubicin-induced Heart Toxicity
Apigenin is a natural part of plants, fruits, and vegetables. It has been shown to be anti-inflammatory, anti-apoptotic, anti-carcinogenic, and an antioxidant. Apigenin has been shown to inhibit CD38, an enzyme that consumes NAD+, and have beneficial effects on animal models of obesity, heart ischemia, kidney injury, viral infection, and cancer.
Not only can apigenin reduce oxidative stress and significantly boost the activity of antioxidant enzymes, it has been observed that apigenin has potential benefits for cardiovascular illnesses owing to the diminution of pro-apoptotic protein activity, the reduction of oxidative stress, and the amelioration of damage to cell energy-producing structures (mitochondria). Therefore, researchers have proposed that this natural substance is suited for medicinal use.
Among many metal nanostructures in recent years, there has been much interest in gold nanoparticles as diagnostic agents and therapeutic applications. Techniques using plant phytochemicals to generate gold nanoparticles are inexpensive, environmentally friendly, and clinically safe. In prior investigations, plant extracts, including apigenin, have been used.
In this study, researchers from the Iran University of Medical Sciences in Tehran examined whether apigenin-coated gold nanoparticles made with phytochemicals could reduce the damage to the heart caused by doxorubicin.
To study the protective effect of apigenin-coated gold nanoparticles on hearts treated with doxorubicin, the researchers injected the anti-tumor agent for 12 days into rats to cause cardiotoxicity. This treatment was accompanied by increased mortality, heart damage, and cardiomyocyte apoptosis, as well as decreased heart and body weight. The synthesized apigenin-coated gold nanoparticles, which were on average 21 nm in size, were stable for four weeks in a saline solution.
Using a test called the MTT, which measures cellular metabolic activity as an indicator of cell viability, proliferation, and cytotoxicity. The researchers found that one day of treatment of heart cells with apigenin-coated gold nanoparticles was non-toxic, making them appropriate for therapeutic applications. More importantly, treatment with apigenin-coated gold nanoparticles reversed all of the negative effects of doxorubicin on heart and body weight, heart damage, and cardiomyocyte apoptosis.
The researchers propose that therapy with apigenin-coated gold nanoparticles minimizes heart and body weight loss by reducing cardiomyocyte loss, enhancing food intake, and reducing the formation of cellular bubbles called vacuoles. The researchers found that reduced apoptosis of cardiomyocytes underlies the beneficial effects of apigenin-coated gold nanoparticles of doxorubicin-treated rats.
This study may provide a novel therapeutic avenue for doxorubicin in cancer therapy. Investigation of the chronic effects of apigenin-covered gold nanoparticles in doxorubicin-induced cardiotoxicity in large animal models while scrutinizing other signaling pathways and functional parameters of the heart would be of value.
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