Dietary selenium for the mitigation of radiation injury: effects of selenium dose escalation and timing of supplementation. Radiat Res 2011 Sep;176(3):366-74
Date
08/27/2011Pubmed ID
21867430Pubmed Central ID
PMC3237945DOI
10.1667/rr2456.1Scopus ID
2-s2.0-80052159464 (requires institutional sign-in at Scopus site) 31 CitationsAbstract
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.
Author List
Sieber F, Muir SA, Cohen EP, Fish BL, Mäder M, Schock AM, Althouse BJ, Moulder JEAuthor
Fritz Sieber PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDiet
Dose-Response Relationship, Drug
Drug Administration Schedule
Humans
Radiation Injuries
Rats
Selenium
