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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1 September 2011
Research Article|
July 08 2011
Dietary Selenium for the Mitigation of Radiation Injury: Effects of Selenium Dose Escalation and Timing of Supplementation
Fritz Sieber
;
Fritz Sieber
1
a Department of Pediatrics and Children's Research Institute
1 Address for correspondence: Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226; e-mail: fsieber@mcw.edu.
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Sarah A. Muir
;
Sarah A. Muir
a Department of Pediatrics and Children's Research Institute
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Eric P. Cohen
;
Eric P. Cohen
c Department of Medicine, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295
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Brian L. Fish
;
Brian L. Fish
b Department of Radiation Oncology and Center for Medical Countermeasures Against Radiological Terrorism, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
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Marylou Mäder
;
Marylou Mäder
b Department of Radiation Oncology and Center for Medical Countermeasures Against Radiological Terrorism, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
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Ashley M. Schock
;
Ashley M. Schock
b Department of Radiation Oncology and Center for Medical Countermeasures Against Radiological Terrorism, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
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Bryan J. Althouse
;
Bryan J. Althouse
b Department of Radiation Oncology and Center for Medical Countermeasures Against Radiological Terrorism, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
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John E. Moulder
John E. Moulder
b Department of Radiation Oncology and Center for Medical Countermeasures Against Radiological Terrorism, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
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Radiat Res (2011) 176 (3): 366–374.
Article history
Received:
September 27 2010
Accepted:
June 07 2011
Citation
Fritz Sieber, Sarah A. Muir, Eric P. Cohen, Brian L. Fish, Marylou Mäder, Ashley M. Schock, Bryan J. Althouse, John E. Moulder; Dietary Selenium for the Mitigation of Radiation Injury: Effects of Selenium Dose Escalation and Timing of Supplementation. Radiat Res 1 September 2011; 176 (3): 366–374. doi: https://doi.org/10.1667/RR2456.1
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