High-Dose Selenium for the Mitigation of Radiation Injury: A Pilot Study in a Rat Model

Sieber, Fritz; Muir, Sarah A.; Cohen, Eric P.; North, Paula E.; Fish, Brian L.; Irving, Amy A.; Mäder, Marylou; Moulder, John E.

doi:10.1667/0033-7587-171.3.368

Cited by 39 publications

(29 citation statements)

References 18 publications

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“…4b, Table 2). Similar glomerular lesions have been described previously (Sieber et al 2009;Caloglu et al 2009). Kidney lesions were obvious in the cortex 64 d post-irradiation, but analysis revealed that deeper lesions developed between 64 and 104 d after irradiation, as shown by the increased histological score in the medulla between 64 and 104 d post-irradiation (Table 2).…”

Section: Evolution Of Body Weight In 12-gy and 14-gy Irradiated Rats supporting

confidence: 87%

Experimental Quantification of Delayed Radiation-Induced Organ Damage in Highly Irradiated Rats With Bone Marrow Protection

Boittin¹,

Martigne²,

Mayol³

et al. 2015

Health Physics

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The evolution of organ damage following extensive high-dose irradiation remains largely unexplored and needs further investigation. Wistar rats [with or without partial bone marrow protection (∼20%)] were irradiated at lethal gamma-ray doses (12, 14, and 16 Gy) and received antibiotic support. While total-body-irradiated rats did not survive, bone marrow protection (achieved by protecting hind limbs behind a lead wall) combined with antibiotic support allowed survival of 12-Gy and 14-Gy irradiated rats for more than 3 mo, with a late phase of body weight loss and altered clinical status. Histological analysis of radiation-induced damages in visceral organs (liver, kidney, and ileum), performed 64 and 104 d after high-dose body irradiation, indicates that the extent and the evolution of damage depend on both the irradiation dose and organ. A dose-related aggravation of lesions was observed in the liver and kidney but not in the ileum. In contrast to the liver, alterations in the kidney and ileum aggravate with time, emphasizing the need to develop new efficient countermeasures to protect both the gastrointestinal tract and kidney from late-occurring radiation effects. Specifically, the complex evolution of organ damage presented in this paper offers the possibility to explore and then validate specific therapeutic windows using candidate drugs targeted to each injured visceral organ.

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Section: Evolution Of Body Weight In 12-gy and 14-gy Irradiated Rats supporting

confidence: 87%

Experimental Quantification of Delayed Radiation-Induced Organ Damage in Highly Irradiated Rats With Bone Marrow Protection

Boittin¹,

Martigne²,

Mayol³

et al. 2015

Health Physics

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“…Sieber et al (15) showed that dietary supplementation with selenium at high doses immediately after 10 Gy total body irradiation exposure decreased significantly radiation damage to kidneys. Those authors administered a dose of 10.95 µg/mL per day of sodium selenite dissolved in distilled water, and the total dose during the whole experimental period was 0.2 mg.…”

Section: Discussionmentioning

confidence: 99%

Effect of sodium selenite on bone repair in tibiae of irradiated rats

et al. 2009

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This study evaluated the radioprotective effect of sodium selenite on the bone repair process in tibiae of female rats. For such purpose, 100 female Wistar rats (Rattus norvegicus, albinus) were randomly assigned to 4 groups (n=25), according to the treatment received: administration of distilled water (control); administration of sodium selenite; gamma radiation; and administration of sodium selenite plus gamma radiation. A bone defect was prepared on both tibiae of all animals. Three days after surgery, the gamma radiation and selenium/gamma radiation groups received 8 Gy gamma rays on the lower limbs. Five animals per group were sacrificed 7, 14, 21, 28 days after surgery for evaluation of the repair process by bone volumetric density analysis. The 5 animals remaining in each group were sacrificed 45 days postoperatively for examination of the mature bone by scanning electron microscopy. Based on all analyzed parameters, the results of the present study suggest that sodium selenite exerted a radioprotective effect in the bone repair of tibia of irradiated rats.

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“…We recently reported that dietary supplementation with high-dose selenium in the form of sodium selenite or seleno-L-methionine initiated immediately after total-body irradiation (TBI; 10 Gy, single dose) and maintained for 21 weeks reduces radiation injury to kidneys in a rat model (1). Irradiated rats on selenium-supplemented drinking water had lower blood urea nitrogen (BUN) levels and showed fewer histopathological abnormalities than age-matched irradiated rats on standard drinking water.…”

Section: Introductionmentioning

confidence: 99%

Dietary Selenium for the Mitigation of Radiation Injury: Effects of Selenium Dose Escalation and Timing of Supplementation

Sieber

Muir²,

Cohen

et al. 2011

Radiation Research

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We recently reported that daily dietary supplementation with 100 μg selenium (a dose exceeding a rat’s nutritional requirement by about 33-fold) initiated immediately after total-body irradiation (TBI) and maintained for 21 weeks mitigates radiation nephropathy in a rat model as indicated by blood urea nitrogen (BUN) levels and histopathological criteria (Radiat Res. 2009; 17:368–73). In this follow-up study, we explored the risks and benefits of delaying the onset of supplementation, shortening periods of supplementation, and escalating selenium supplementation beyond 100 μg/day. Supplementation with 200 μg selenium/day (as selenite or seleno-L-methionine) substantially improved the mitigation of radiation nephropathy by lowering BUN levels at 4 months after TBI from 115 to as low as 34 mg/dl and by proportionally lowering the incidence of histopathological abnormalities. Shortening the period of supplementation to 3 or 2 months did not compromise efficacy. Delaying the onset of supplementation for 1 week reduced but did not abrogate the mitigation of radiation nephropathy. Supplementation with 300 μg/day mitigated radiation nephropathy less effectively than 200 μg and was poorly tolerated. Rats that had been given 10 Gy of TBI were less tolerant of high-dose selenium than nonirradiated rats. This reduced tolerance of high-dose selenium would need to be taken into consideration when selenium is used for the mitigation of radiation injury in victims of nuclear accidents or acts of radiological terrorism. The high dose requirements, the pronounced threshold effect, and the superior performance of selenite suggest that the mitigation of radiation nephropathy involves mechanisms that go beyond the induction of selenoproteins.

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High-Dose Selenium for the Mitigation of Radiation Injury: A Pilot Study in a Rat Model

Cited by 39 publications

References 18 publications

Experimental Quantification of Delayed Radiation-Induced Organ Damage in Highly Irradiated Rats With Bone Marrow Protection

Experimental Quantification of Delayed Radiation-Induced Organ Damage in Highly Irradiated Rats With Bone Marrow Protection

Effect of sodium selenite on bone repair in tibiae of irradiated rats

Dietary Selenium for the Mitigation of Radiation Injury: Effects of Selenium Dose Escalation and Timing of Supplementation

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