Dr. Ron’s Research Review – October 25, 2017

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This week’s research review focuses on Nuclear Radiation Emergency protection.

 

Potassium Iodide (KI)

In a breach-of-containment nuclear reactor accident, the near-field exposure is primarily through inhalation of radioiodine. Thyroid blockade by oral potassium iodide (KI) is a practical and effective protective measure for the general public in such an emergency. Boxes of ten 130 mg KI tablets have been distributed in France. (Jang et al., 2008)

Melatonin

Melatonin may be useful to scavenge a variety of free radicals, including the hydroxyl radical induced by ionizing radiation. (Vijayalaxmi et al., 2004)

Flaxseed

Flaxseed has received a lot of attention and has been found to be equally effective when administered before or after irradiation, and against low doses (≤ 5 Gy) to the whole body or high doses (12-13.5 Gy) to the whole thorax. (Kma, 2014) (Pietrofesa et al., 2013)

Plant Extracts

Radiation exposure leads to several pathophysiological conditions, including oxidative damage, inflammation and fibrosis, thereby affecting the survival of organisms. Several plant extracts may be useful. (Kma, 2014)
Curcumin
Picrorhiza kurroa and Podophyllum hexandrum
Chelidonium majus and Ukrain, its alkaloid thiophosphoric acid derivative
Mentha piperita

 

Dr. Ron

 


Articles

 

Thyroid dose estimation with potassium iodide (KI) administration in a nuclear emergency.
            (Jang et al., 2008) Download
In a breach-of-containment nuclear reactor accident, the near-field exposure is primarily through inhalation of radioiodine. Thyroid blockade by oral potassium iodide (KI) is a practical and effective protective measure for the general public in such an emergency. The retention functions incorporating the thyroid blocking effects by KI have been derived using a standard three-compartment model of iodine metabolism. This allows more accurate estimation of the thyroid dose by calculating the blocking factor.

Plant extracts and plant-derived compounds: promising players in a countermeasure strategy against radiological exposure.
            (Kma, 2014) Download
Radiation exposure leads to several pathophysiological conditions, including oxidative damage, inflammation and fibrosis, thereby affecting the survival of organisms. This review explores the radiation countermeasure properties of fourteen (14) plant extracts or plant-derived compounds against these cellular manifestations. It was aimed at evaluating the possible role of plants or its constituents in radiation countermeasure strategy. All the 14 plant extracts or compounds derived from it and considered in this review have shown some radioprotection in different in vivo, ex-vivo and or in vitro models of radiological injury. However, few have demonstrated advantages over the others. C. majus possessing antioxidant, anti-inflammatory and immunomodulatory effects appears to be promising in radioprotection. Its crude extracts as well as various alkaloids and flavonoids derived from it, have shown to enhance survival rate in irradiated mice. Similarly, curcumin with its antioxidant and the ability to ameliorate late effect of radiation exposure, combined with improvement in survival in experimental animal following irradiation, makes it another probable candidate against radiological injury. Furthermore, the extracts of P. hexandrum and P. kurroa in combine treatment regime, M. piperita, E. officinalis, A. sinensis, nutmeg, genistein and ginsan warrants further studies on their radioprotective potentials. However, one that has received a lot of attention is the dietary flaxseed. The scavenging ability against radiation-induced free radicals, prevention of radiation-induced lipid peroxidation, reduction in radiation cachexia, level of inflammatory cytokines and fibrosis, are some of the remarkable characteristics of flaxseed in animal models of radiation injury. While countering the harmful effects of radiation exposure, it has shown its ability to enhance survival rate in experimental animals. Further, flaxseed has been tested and found to be equally effective when administered before or after irradiation, and against low doses (≤ 5 Gy) to the whole body or high doses (12-13.5 Gy) to the whole thorax. This is particularly relevant since apart from the possibility of using it in pre-conditioning regime in radiotherapy, it could also be used during nuclear plant leakage/accidents and radiological terrorism, which are not pre-determined scenarios. However, considering the infancy of the field of plant-based radioprotectors, all the above-mentioned plant extracts/plant-derived compounds deserves further stringent study in different models of radiation injury.

Radiation mitigating properties of the lignan component in flaxseed.
            (Pietrofesa et al., 2013) Download
BACKGROUND:  Wholegrain flaxseed (FS), and its lignan component (FLC) consisting mainly of secoisolariciresinol diglucoside (SDG), have potent lung radioprotective properties while not abrogating the efficacy of radiotherapy. However, while the whole grain was recently shown to also have potent mitigating properties in a thoracic radiation pneumonopathy model, the bioactive component in the grain responsible for the mitigation of lung damage was never identified. Lungs may be exposed to radiation therapeutically for thoracic malignancies or incidentally following detonation of a radiological dispersion device. This could potentially lead to pulmonary inflammation, oxidative tissue injury, and fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in a mouse model of radiation pneumonopathy. METHODS:  We evaluated FLC-supplemented diets containing SDG lignan levels comparable to those in 10% and 20% whole grain diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC) were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4 months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and oxidative damage levels, and survival. RESULTS:  FLC significantly mitigated radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7% survival 4 months post-XRT compared to 60-73.3% survival in mice fed 10%-20% FLC initiated 24-72 hours post-XRT. FLC also mitigated radiation-induced lung fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased fibrosis as compared to mice fed control diet while the corresponding TGF-beta1 levels detected immunohistochemically were also decreased. Additionally, 10-20% FLC initiated at any time point post radiation exposure, mitigated radiation-induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly, neutrophilic and overall inflammatory cell infiltrate in airways and levels of nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively) were also mitigated by the lignan diet. CONCLUSIONS:  Dietary FLC given early post-XRT mitigated radiation effects by decreasing inflammation, lung injury and eventual fibrosis while improving survival. FLC may be a useful agent, mitigating adverse effects of radiation in individuals exposed to incidental radiation, inhaled radioisotopes or even after the initiation of radiation therapy to treat malignancy.


 

Melatonin as a radioprotective agent: a review.
            (Vijayalaxmi et al., 2004) Download
Melatonin (N-acetyl-5-methoxytryptamine), the chief secretory product of the pineal gland in the brain, is well known for its functional versatility. In hundreds of investigations, melatonin has been documented as a direct free radical scavenger and an indirect antioxidant, as well as an important immunomodulatory agent. The radical scavenging ability of melatonin is believed to work via electron donation to detoxify a variety of reactive oxygen and nitrogen species, including the highly toxic hydroxyl radical. It has long been recognized that the damaging effects of ionizing radiation are brought about by both direct and indirect mechanisms. The direct action produces disruption of sensitive molecules in the cells, whereas the indirect effects ( approximately 70%) result from its interaction with water molecules, which results in the production of highly reactive free radicals such as *OH, *H, and e(aq)- and their subsequent action on subcellular structures. The hydroxyl radical scavenging ability of melatonin was used as a rationale to determine its radioprotective efficiency. Indeed, the results from many in vitro and in vivo investigations have confirmed that melatonin protects mammalian cells from the toxic effects of ionizing radiation. Furthermore, several clinical reports indicate that melatonin administration, either alone or in combination with traditional radiotherapy, results in a favorable efficacy:toxicity ratio during the treatment of human cancers. This article reviews the literature from laboratory investigations that document the ability of melatonin to scavenge a variety of free radicals (including the hydroxyl radical induced by ionizing radiation) and summarizes the evidence that should be used to design larger translational research-based clinical trials using melatonin as a radioprotector and also in cancer radiotherapy. The potential use of melatonin for protecting individuals from radiation terrorism is also considered.

 

References

Jang, M, et al. (2008), ‘Thyroid dose estimation with potassium iodide (KI) administration in a nuclear emergency.’, Radiat Prot Dosimetry, 132 (3), 303-7. PubMed: 19054795
Kma, L (2014), ‘Plant extracts and plant-derived compounds: promising players in a countermeasure strategy against radiological exposure.’, Asian Pac J Cancer Prev, 15 (6), 2405-25. PubMed: 24761841
Pietrofesa, R, et al. (2013), ‘Radiation mitigating properties of the lignan component in flaxseed.’, BMC Cancer, 13 179. PubMed: 23557217
Vijayalaxmi, et al. (2004), ‘Melatonin as a radioprotective agent: a review.’, Int J Radiat Oncol Biol Phys, 59 (3), 639-53. PubMed: 15183467