Dietary selenium for the mitigation of radiation injury: effects of selenium dose escalation and timing of supplementation
| Autor: | Brian L. Fish, Fritz Sieber, Bryan J. Althouse, Sarah A. Muir, John E. Moulder, Marylou Mäder, Eric P. Cohen, Ashley M. Schock |
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| Rok vydání: | 2011 |
| Předmět: |
Radiation Nephropathy
medicine.medical_specialty Biophysics Physiology chemistry.chemical_element Drug Administration Schedule Article Selenium Dose escalation Medicine Animals Humans Radiology Nuclear Medicine and imaging Dietary supplementation Radiation Injuries Blood urea nitrogen Radiation injury Radiation Dose-Response Relationship Drug business.industry Dietary Selenium Surgery Diet Rats Dose–response relationship chemistry business |
| Zdroj: | Radiation research. 176(3) |
| ISSN: | 1938-5404 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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