Radiation therapy is a crucial component of cancer treatment, but it can have damaging side effects on healthy cells. The use of radioprotective agents to minimize the harmful effects of radiation is an area of active research. Natural compounds, particularly polyphenols, have shown promising protective effects against radiation damage, offering a potential solution for improving treatment outcomes and reducing side effects.
Polyphenols are a group of natural compounds found in fruits, vegetables, and herbs that possess antioxidant and anti-inflammatory properties. These compounds can scavenge free radicals and modulate cell signaling pathways, thereby protecting normal cells from the harmful effects of ionizing radiation. Additionally, polyphenols have been shown to enhance DNA repair processes, further contributing to their radioprotective potential.
In this article, we will explore the role of polyphenols and other natural compounds as radioprotective agents in cancer treatment. We will discuss the specific polyphenols that have been studied for their radioprotective properties, including curcumin, epigallocatechin gallate (EGCG), resveratrol, quercetin, luteolin, and more. We will examine the scientific evidence supporting their use, their mechanisms of action, and potential applications in combination with radiation therapy.
Key Takeaways:
- Polyphenols, including curcumin, EGCG, resveratrol, quercetin, luteolin, and others, have shown potential as radioprotective agents.
- These natural compounds possess antioxidant and anti-inflammatory properties that can protect normal cells from radiation-induced damage.
- Polyphenols may enhance DNA repair processes, further contributing to their radioprotective effects.
- Understanding the mechanisms of action and cell signaling pathways involved in radioprotection can help optimize their use in cancer treatment.
- The use of natural radioprotective agents holds promise for improving treatment outcomes and reducing the side effects of radiation therapy.
Introduction
In this section, we will provide an introduction to the topic of radioprotective agents and their role in mitigating the effects of radiation. We will begin by explaining the basics of radiation, including the different types of radiation and their sources. We will then delve into the various harmful effects of radiation on the body, such as DNA damage, cell death, and oxidative stress. Next, we will discuss the concept of radioprotection and how it involves the use of natural compounds to minimize the detrimental effects of radiation. We will explore the mechanisms by which these natural compounds exert their protective effects, including their ability to scavenge free radicals, modulate cell signaling pathways, and enhance DNA repair processes. By understanding these mechanisms, we can gain insights into the therapeutic potential of natural compounds as radioprotective agents.
Understanding Radiation and Its Effects
Before delving into the role of natural compounds in radioprotection, it is important to have a basic understanding of radiation and its effects on the body. Radiation can be classified into two main types: ionizing radiation and non-ionizing radiation. Ionizing radiation, such as X-rays and gamma rays, has sufficient energy to remove tightly bound electrons from atoms, leading to the formation of ions. This ionization process can cause damage to DNA and other cellular structures.
Exposure to ionizing radiation can result in a range of harmful effects, including DNA damage, cell death, and oxidative stress. One of the primary mechanisms by which ionizing radiation causes cellular damage is through the generation of free radicals. Free radicals are highly reactive molecules that can react with and damage DNA, proteins, and lipids, leading to cellular dysfunction and potential long-term health effects.
The Role of Natural Compounds in Radioprotection
Radioprotection involves the use of natural compounds to minimize the detrimental effects of radiation on the body. These natural compounds, including polyphenols, carotenoids, vitamins, minerals, and herbal extracts, possess antioxidant and anti-inflammatory properties that can help mitigate radiation-induced damage.
One of the key mechanisms by which natural compounds exert their radioprotective effects is through their ability to scavenge free radicals. Free radicals are a major contributor to radiation-induced cellular damage, and natural compounds can help neutralize these reactive molecules, protecting cells from oxidative stress.
Natural compounds also have the ability to modulate cell signaling pathways that are involved in radiation damage. By influencing these pathways, natural compounds can regulate cell survival, DNA repair, and cellular responses to radiation, thereby mitigating the harmful effects of ionizing radiation.
Furthermore, natural compounds have been shown to enhance DNA repair processes, promoting the restoration of damaged DNA caused by radiation. This can help maintain genomic stability and minimize the risk of long-term health effects arising from radiation exposure.
Overall, the use of natural compounds as radioprotective agents holds immense potential in mitigating the harmful effects of radiation and improving treatment outcomes. By harnessing the antioxidant, anti-inflammatory, and cell signaling modulatory properties of these natural compounds, we can enhance the body’s ability to protect itself against radiation-induced damage.
Polyphenols as Radioprotective Agents
In this section, we will explore the radioprotective properties of polyphenols, a group of natural compounds widely distributed in plants. Polyphenols have gained significant attention due to their antioxidant and anti-inflammatory effects, which make them promising candidates for radiation protection.
Curcumin: The Golden Spice of Protection
Curcumin, derived from the spice turmeric, has been extensively studied for its radioprotective properties. It possesses potent antioxidant and anti-inflammatory effects, which can help mitigate radiation-induced damage. By scavenging free radicals and modulating cell signaling pathways, curcumin has shown the potential to protect normal cells from the harmful effects of ionizing radiation during cancer treatment.
curcumin has been demonstrated to exert radioprotective effects by scavenging ROS and inhibiting lipid peroxidation [175]. In addition, as a free-radical scavenger, curcumin can increase the activity of antioxidant enzymes, such as SOD, CAT, and glutathione peroxidase [176]. Another study demonstrated that curcumin can regulate the inflammatory factor levels, including that of IL-1, IL-6, interleukin-18 (IL-18), and TNF-α; thus, providing protection against radiation-induced damage [30]. Additionally, curcumin has been shown to protect the brain from carbon ion irradiation-induced irreversible cerebral injuries, including learning and memory defects [177]. (Zhang 2023)
Not only a radioprotective agent, Curcumin also stars a s a radisensitizing agent.
curcumin is capable to enhance the cytotoxicity of temozolomide in GBM cells [36]. Our results concluded that, similar to those reported in human glioma U251 cells [38,39], curcumin can cause G2/M arrest in glioma F98 cells and increase the sensitivity of glioma cells to radiation (Wang 2020)
Epigallocatechin Gallate (EGCG): The Power of Green Tea
Epigallocatechin gallate (EGCG), abundant in green tea, is another polyphenol that exhibits remarkable radioprotective properties. With its potent antioxidant and anti-inflammatory activities, EGCG can help counteract radiation-induced cellular damage. It has been shown to enhance DNA repair mechanisms and protect against radiation-induced oxidative stress, showcasing its potential in improving treatment outcomes while reducing side effects.
we demonstrated that epigallocatechin gallate (EGCG) could inhibit effectively IR-induced (Ionizing Radiation) damage to mouse normal hepatic cells AML-12, and improve dramatically the radiosensitivity of mouse hepatoma cells H22 to 60Coγ.
radiation protection and radiosensitization of EGCG were associated with apoptosis regulated by miR-34a/Sirt1/p53 signaling pathway. (Kang 2019)
Resveratrol and GSE: Grapes answer to Radiation Damage
Resveratrol, commonly found in grapes and red wine, has garnered attention for its antioxidant and anti-inflammatory effects. This polyphenol has been shown to reduce radiation-induced DNA damage and cellular damage caused by ionizing radiation. By reducing oxidative stress and inflammation, resveratrol holds promise as a natural radioprotective agent in cancer treatment. Additionally, like Curcumin, it also acts as a radiosensitizer against cancer cells.
Resveratrol, in addition to its well-documented properties in the prevention of age-related diseases and aging, has been extensively studied in terms of radiotherapy. However, in this case, resveratrol has a double face. On one hand, it can increase the radioresistance of cells, which is very beneficial in protecting healthy tissues during radiotherapy. On the other hand, many studies show that it can increase the sensitivity of cancer cells to radiation (Komorowska 2022)
Grape Seed Extract (GSE) is another Grape product showing great promise as a radioprotective agent.
Remarkable reduction in micronuclei frequency was due to the high antioxidant and free-radical scavenging abilities of Grape Seed Extract (GSE). The protective effect of GSE was dose- and time-dependent; the most protective effect was seen 2 hr following oral administrations of GSE 1000 mg (51.73% reduction in the incidence of micronuclei).
The results revealed that oral administration of GSE before irradiation, leads to the reduction of DNA damages in human’s blood lymphocytes; in addition, GSE did not show cytogenetic and toxic effects at different doses. Based on the results, it is suggested that oral administration of GSE before different medical interventions such as computed tomography, radiography, nuclear imaging, and radiotherapy, could be beneficial. (Targhi 2020)
Quercetin: The Protector in Apples and Onions
Quercetin, present in apples and onions, is a versatile polyphenol that possesses potent antioxidant and anti-inflammatory properties. It is known for its ability to protect against radiation-induced DNA damage, reduce oxidative stress, and modulate various cellular signaling pathways. Quercetin’s radioprotective potential makes it an intriguing natural compound for further exploration in cancer treatment.
Another example is quercetin, which is known for its antioxidative properties and is widely distributed in plants. Quercetin helps protect against radiation-induced DNA damage by enhancing the cellular antioxidant defense systems and promoting the repair of DNA strand breaks [57,58]. (Zhang 2023)
Luteolin: The Lesser-Known Guardian
Luteolin, found in various fruits and vegetables, is another polyphenol with remarkable radioprotective potential. It exhibits strong antioxidant and anti-inflammatory properties, which can help protect cells from radiation-induced damage. By scavenging free radicals and modulating cell signaling pathways, luteolin shows promise in enhancing the efficacy of cancer treatment while minimizing side effects.
Luteolin’s anticancer property is associated with the induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis. Furthermore, luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3′-kinase (PI3K)/Akt, nuclear factor kappa B (NF-κB), and X-linked inhibitor of apoptosis protein (XIAP), and stimulating apoptosis pathways including those that induce the tumor suppressor p53. (Lin 2023)
Genistein
Genistein (4′,5,7-trihydroxyisoflavone), a soy isoflavone, has been shown to play a role in radioprotection [107,108]. The radioprotective effects of genistein are mediated by several mechanisms, including free-radical scavenging, anti-inflammatory effects, and activation of DNA repair enzymes [109]. Genistein has been reported to decrease the hemorrhages, inflammation, and fibrosis caused by radiotherapy [110]. In animal studies, genistein reduced the radiation-induced intestinal damage in tumor-bearing mice [111]. In addition, genistein has been shown to increase the survival rate of mice that receive thoracic radiation [112].
Notably, genistein has been found to have radiosensitizing and anticancer effects, as well as significant radioprotective effects (Zhang 2023)
Carotenoids and Other Antioxidants
In this section, we will explore the role of carotenoids and other antioxidants in radioprotection. Carotenoids are a group of pigments found in various fruits and vegetables that possess potent antioxidant properties. We will focus on three specific carotenoids: astaxanthin, lycopene, and beta-carotene.
Astaxanthin: The Super Antioxidant from the Sea
Astaxanthin, derived from microalgae and seafood, is known for its exceptional antioxidant capacity and has been shown to protect against radiation-induced damage. Its powerful antioxidant properties allow it to neutralize harmful free radicals in the body, reducing oxidative stress and preventing cellular damage caused by ionizing radiation.
he results show that Astaxanthin improved TBI-induced skewed differentiation of peripheral blood cells and ameliorated BM suppression by accelerating hematopoietic self-renewal and regeneration. These findings were associated with the scavenging of ROS according to Nrf2-mediated increased activation of anti-oxidant proteins. Further study showed that the reduction of apoptosis in c-kit positive cells by regulating apoptotic-related proteins is also attributable to the radioprotective effects of ATX. (Xue 2017)
Lycopene: The Radioprotective Red Pigment
Lycopene is a pigment responsible for the red color of tomatoes and other fruits. It exhibits strong antioxidant properties and has demonstrated radioprotective effects. Lycopene can scavenge free radicals generated by radiation, thereby reducing oxidative damage to cells and protecting against radiation-induced DNA damage.
Beta-Carotene: The Pre-Vitamin A Shield
Beta-carotene, a precursor of vitamin A found in carrots and other orange-colored fruits and vegetables, serves as a potent antioxidant and can help shield cells from radiation damage. Its antioxidant properties enable it to neutralize free radicals and protect against radiation-induced oxidative stress, thereby reducing the risk of DNA damage and cellular injury.
Vitamins and Minerals
In this section, we will explore the role of vitamins and minerals as radioprotection.
In addition, the radioprotective properties of several naturally occurring vitamins and dietary antioxidants have been tested [213]. For example, α-lipoic acid significantly increased mouse survival rates following lethal total body irradiation. Furthermore, vitamins A, C, E, and β-carotene have been found to increase radiation resistance [214]. Clearly, vitamins act as cofactors and regulate many physiological systems in addition to their radioprotective activities. (Zhang 2023)
Vitamin C: The Essential Antioxidant
Vitamin C, also known as ascorbic acid, is a powerful antioxidant that can mitigate the damaging effects of radiation-induced free radicals. It plays a vital role in neutralizing these harmful molecules and protecting cells from oxidative stress caused by radiation. Vitamin C’s antioxidant properties can help prevent cellular damage and DNA mutations, contributing to radioprotection. Additionally, it has been shown to enhance DNA repair mechanisms, further supporting its role in minimizing the negative effects of radiation.
Our findings confirm the results obtained in our previous study which investigated the survival rate in animals received vitamin C 1h, 12h and 24h after irradiation. This study showed that vitamin C can potentially be used up to 24 hours after exposure to high levels of ionizing radiation in life threatening situations such as unpredictable solar particle events. … The significant radioprotective effect of vitamin C at doses used in this study opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation. (Mortazavi 2015)
Vitamin E: The Fat-Soluble Protector
Vitamin E is a fat-soluble vitamin that acts as a membrane stabilizer and scavenges free radicals, providing protection against radiation-induced damage. As an antioxidant, it plays a crucial role in preventing the oxidation of lipids and other biomolecules, which can lead to cellular damage. By neutralizing free radicals, vitamin E helps maintain the integrity of cell membranes and supports overall cellular function. Its ability to scavenge reactive oxygen species contributes to radioprotection and may enhance DNA repair processes.
Minerals and Trace Elements
In this section, we will explore the importance of minerals and trace elements as radioprotective agents. Two specific elements that will be focused on are selenium and zinc.
Selenium: The Trace Element Shield
Selenium is an essential trace element that plays a crucial role in antioxidant defense and DNA repair. As a radioprotective agent, selenium has shown promising effects in protecting cells from radiation-induced damage. Its ability to scavenge free radicals and enhance DNA repair processes contribute to its radioprotective properties.
Both in acute and long‐term side effects of radiotherapy, selenium has been discussed as a preventive agent. In vitro experiments found a cytoprotective effect of sodium selenite on human fibroblasts and endothelial cells without reducing radiotherapy activity against cancer cells (Rodemann 1999; Schleicher 1999). Sagowski 2004 showed that administration of parenteral sodium selenite reduced radiogenic damage to parotid glands in rats, which was confirmed by better gland function after irradiation. (Denert 2006)
Both amifostine and sodium selenite protected chondrocytes and osteoblasts from the negative effects of irradiation, while not protecting the tumor cells. The pediatric tumor cell lines were generally more radiosensitive than the bone cells examined. The radioprotectant drugs amifostine and sodium selenite provided significant radioprotection to constituent bone cells while not protecting the tumor cells. Finally, amifostine and sodium selenite therapy provided an additional benefit beyond radioprotection by increasing cytotoxicity in nonirradiated and irradiated tumor cells. (Margulies 2008)
Zinc: The Essential Mineral for DNA Repair
Zinc, an essential mineral, is involved in various cellular processes, including DNA repair. It plays a vital role in maintaining DNA integrity and stability. Zinc’s ability to support DNA repair mechanisms makes it an important mineral in radioprotection. By aiding in the repair of DNA damage caused by radiation, zinc can help protect cells from cellular damage and promote overall health.
We will discuss the scientific evidence supporting the radioprotective effects of these minerals and trace elements, their mechanisms of action, and their potential applications in cancer treatment.
Herbal Extracts and Their Compounds
In this section, we will explore the radioprotective properties of herbal extracts and their compounds. Specifically, we will focus on three key herbal extracts: ginseng, milk thistle, and garlic, and the compounds they contain.
Ginsenosides: The Radioprotective Ginseng Extracts
Ginseng, a popular herbal remedy, contains bioactive compounds called ginsenosides. These ginsenosides have been extensively studied for their antioxidant and radioprotective properties. Research has shown that ginseng extracts can help protect cells from radiation-induced cellular damage. By scavenging free radicals and reducing oxidative stress, ginsenosides can potentially mitigate the harmful effects of radiation on the body.
In this study, the number of Sca-1+ HSC/HPCs (hematopoietic stem/progenitor cells) was violently reduced following exposure to 6.5 Gy X-ray TBI, and these levels barely recovered; however, in the irradiated+Rg1 group, a notable increase in the number of cells was observed on d 3 (Figure 1). This result suggests that ionizing irradiation is fatal to HSC/HPCs, but ginsenoside Rg1 can help restore the HSC/HPCs.
Administration of ginsenoside Rg1 enhances the resistance of HSC/HPCs to ionizing radiation-induced senescence in mice by inhibiting the oxidative stress reaction, reducing DNA damage, and regulating the cell cycle. (Chen 2014)
Silymarin: The Liver-Protecting Milk Thistle Compound
Milk thistle, known for its liver-protecting effects, contains an active component called silymarin. Silymarin has also demonstrated radioprotective properties. It acts as a powerful antioxidant, helping to neutralize free radicals and reduce oxidative stress caused by radiation. Additionally, silymarin has been shown to enhance the repair of DNA damage caused by radiation, further contributing to its radioprotective benefits.
The findings revealed that the ionizing radiation-treated groups had reduced survival rates and body weight in comparison with the control groups. It was also found that radiation can induce mild to severe adverse effects on the skin, digestive, hematologic, lymphatic, respiratory, reproductive, and urinary systems. Nevertheless, the administration of silymarin/silibinin could mitigate the ionizing radiation-induced adverse effects in most cases. This herbal agent exerts its radioprotective effects through anti-oxidant, anti-apoptosis, anti-inflammatory activities, and other mechanisms.
Conclusion: The results of the current systematic review showed that co-treatment of silymarin/silibinin with radiotherapy alleviates the radiotherapy-induced adverse effects in healthy cells/tissues. (Latacella 2023)
Allicin: Garlic’s Contribution to Radioprotection
Garlic, a widely used culinary ingredient, contains a compound called allicin. Allicin exhibits antioxidant and anti-inflammatory effects, making it a potential contributor to radioprotection. Research suggests that allicin can scavenge free radicals and reduce cellular damage caused by radiation. Its anti-inflammatory properties may also help mitigate inflammation induced by radiation, further protecting cells from harm.
S-allyl cysteine sulphoxide (SACS), a sulphur containing aminoacid of garlic is the precursor of allicin and garlic oil, and has been found to show significant radio protective effect in albino rats which were whole body irradiated with 400 rads of irradiation by Cobalt 60 source. It markedly reduced the radiation induced mortality and showed significant protection against the tissue damaging effects of irradiation in histopathological sections of liver and lung. (Jaiswal 1996)
Garlic extract and its chemical constituents such as allicin, alliin, and diallyl sulfide have inhibitory effects on chemical mutagenesis and carcinogenesis [3–5]. Furthermore, experiments in vitro using Salmonella tester strains and Chinese hamster ovary cells showed that garlic exerts an antimutagenic effect against gammaradiation possibly through the scavenging of free radicals [4]. Other researchers also demonstrated a radioprotective effect of garlic against tissue damage in liver and lung, reducing the radiation-induced mortality in albino rats [6]. Based on these observations, some constituents in Allium vegetables such as onions and garlic are expected to be radioprotective.
Melatonin: The Nighttime Radioprotector
neutralization of free radicals produced by IR;melatonin affects several signaling pathways, such as inflammatory responses, antioxidant defense, DNA repair response enzymes, pro-oxidant enzymes. (radioprotectors.org)
Melatonin, a hormone produced by the pineal gland, is known for its role in regulating sleep-wake cycles. However, it also possesses potent antioxidant, anti-inflammatory, and DNA repair properties, making it a promising radioprotective agent. Melatonin’s ability to scavenge free radicals and reduce oxidative stress can help protect against radiation-induced damage. It has been shown to enhance DNA repair processes and support the maintenance of genomic integrity. Additionally, melatonin can modulate immune responses and reduce inflammation, further contributing to its radioprotective effects. (Chang 2012)
Emerging Compounds and Research
In this section, we will explore emerging compounds and ongoing research in the field of radioprotection. We will focus on five specific compounds: sulforaphane, chlorogenic acid, naringin, rosemarinic acid, and spirulina.
Sulforaphane: The Broccoli Compound Fighting Radiation
Sulforaphane, derived from broccoli, is known for its antioxidant and anti-inflammatory effects. Research has shown that sulforaphane has radioprotective properties and the potential to protect against radiation-induced damage. Studies continue to uncover the mechanisms of action and the specific pathways through which sulforaphane exerts its protective effects.
Sulphoraphave is also a radiosensitizing agent:
Our results suggest that combination of Sulphoraphane and Radiation Treatment exerts a more distinct DNA damage and growth inhibition than each treatment alone. SFN seems to be a viable option to improve treatment efficacy of chemoradiation with hopefully higher rates of secondary resectability after neoadjuvant treatment for pancreatic cancer. (Nauman 2017)
Chlorogenic Acid: The Coffee Antioxidant
Chlorogenic acid, found in coffee, exhibits antioxidant properties. It has garnered interest in the field of radioprotection due to its ability to mitigate radiation-induced damage. Ongoing research aims to further explore the potential of chlorogenic acid as a protective agent against the harmful effects of radiation.
Chlorogenic acid (4 μg/mL), a fruit- and vegetable-derived phenolic derivative, protected lymphocytes from 2 Gy irradiation-induced genetic damage [179]. (Tang 2023)
Naringin: The Grapefruit’s Gift
Naringin, abundantly found in grapefruits, (particularly ruby red grapefruit!) possesses antioxidant and anti-inflammatory effects. Its potential radioprotective properties have led to further investigation into its ability to protect against radiation damage. Research is ongoing to elucidate the mechanisms of action through which naringin exerts its protective effects.
Rosemarinic Acid: Rosemary Tea Benefits
Rosemarinic acid, derived from rosemary, exhibits antioxidant and anti-inflammatory properties. Studies suggest that rosemarinic acid may have radioprotective potential, offering protection against the damaging effects of radiation. Ongoing research aims to uncover the specific mechanisms through which rosemarinic acid exerts its protective effects.
Some natural-product-regulated miRNAs in non-cancer tissues may function as radioprotectors [58,59]. For example, rosmarinic acid alleviated radiation-induced pulmonary fibrosis by suppressing inflammation and ROS levels via the upregulation of miR-19b-3p [58], and its radiation targets CCND2 and MAP3K20 were identified (Tang 2023)
Spirulina: The Algae with Radioprotective Powers
Spirulina, a nutrient-rich algae, possesses multiple beneficial properties, including antioxidant and immune-boosting effects. Emerging research suggests that spirulina may have radioprotective powers and the potential to mitigate radiation-induced damage. Ongoing studies aim to further explore the mechanisms of action and the specific applications of spirulina in the context of radioprotection.
Conclusion
In conclusion, the exploration of natural radioprotective agents, such as polyphenols, carotenoids, vitamins, minerals, and herbal extracts, has revealed promising findings in mitigating the damaging effects of radiation therapy in cancer treatment. These natural compounds possess antioxidant and anti-inflammatory properties that can help reduce oxidative stress, protect against DNA damage, and enhance cellular repair processes.
Looking towards the future, there is a growing trend in harnessing the potential of natural radioprotective agents to improve treatment outcomes and minimize the side effects associated with radiation therapy. Ongoing research and scientific studies are uncovering the mechanisms of action and therapeutic benefits of these compounds, paving the way for their integration into cancer treatment protocols.
However, the future of natural radioprotective agents extends beyond the realm of cancer treatment. Incorporating these compounds into daily life can offer protection against oxidative stress and DNA damage caused by various environmental factors. By adopting a balanced and diverse diet that includes a variety of fruits, vegetables, herbs, and other natural sources, individuals can enhance their overall well-being and support radioprotection.
It is important to note that while natural radioprotective agents show great promise, they should not be considered as standalone treatments or replacements for medical advice. Consultation with healthcare professionals is crucial in developing a comprehensive approach to cancer treatment and overall health management.
References
For more information on these and other radioprotective agents, please see Radioprotectors.org