Selenium as an adjuvant for modification of radiation response

Abstract

Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.

Selenium-L-methionine modulates radiation injury and Duox1 and Duox2 upregulation in rat’s heart tissues

“…21 On the day of irradiation, rats were anesthetized using ketamine (80 mg/kg) and xylazine (5 mg/kg). Based on our previous study, 7 using a field size of 25×5 cm 2 with rats placed supine, irradiation was performed using a Cobalt-60 ( 60 Co) gamma ray source with a dose of 15 Gy to their chests at a dose rate of 109 cGy/min and 60 cm source to skin distance (SSD). This dose of radiation was based on a previous study by Ibis et al for evaluating the radioprotective effect of amifostine and L-carnitine on rat’s heart tissues.…”

“…The choice of this time was also based on our previous study. 7 The lower parts of their heart tissues were fixed in 10% formalin for pathological evaluation while their upper parts were frozen for detection of gene expression as well as IL-4 and IL-13 levels.…”

“…5 Infiltration of inflammatory cells such as lymphocytes, macrophages and mast cells is a common manifestation of cardiac injury induced by ionizing radiation. 7 It seems that accumulation of inflammatory cells induces chronic oxidative stress via increasing pro-inflammatory and pro-fibrotic cytokines as well as upregulation genes involved in reduction/oxidation reactions in a positive feedback. Previous studies proposed the increased levels of interleukin-1 (IL-1) and transforming growth factor beta (TGF-β) in heart tissue following exposure to radiation.…”

Redox tolerance and metabolic reprogramming in solid tumors

“…Chronic inflammation in normal cells is known as a common adverse effect of radiotherapy. The stimulatory effect of chronic inflammation on ROS levels and impairing DNA repairing systems in normal cells can cause genomic instability, thus predisposing the normal tissue cells toward tumorigenesis (Lin et al, 2016; Pua et al, 2020); the importance of which is that chronic oxidative stress is considered as a hallmark of genomic instability (Mortezaee, Goradel, et al, 2019), and that inflammation can be an outcome of this chronic oxidative stress (Farhood, Mortezaee, et al, 2019), so there is a positive bidirectional relationship between inflammation and redox activity. The activity of nuclear factor‐κB (NF‐κB) is considered as a sign of chronic inflammation.…”

Nrf2‐modulation by seleno‐hormetic agents and its potential for radiation protection

“…4 Recent studies showed that Se is capable of mitigating radiation toxicity when administered after IR exposure, suggesting that it may have the potential to be used as a "radiomitigator." 8,12 Exposure to IR can occur as an accidental or even intentional event for example in the case of terroristic attacks or during unexpected accidents in nuclear power plants, nuclear warfare, or in industrial plants and research centers in which radioactive probes and isotopes are utilized. Exposure to high-level whole-body irradiation can induce acute radiation syndrome, resulting in symptoms such as nausea, vomiting, fatigue, fever, and diarrhea as well as delayed effects including infection, bleeding and gastrointestinal symptoms.…”