Ketone bodies to protect tissues from damage by ionizing radiation
Described herein is the surprising discovery that ketone bodies protect cell and tissues from ionizing radiation. Based on this finding, methods of protecting animal tissue and cells from damage caused by radiation exposure are disclosed which include, contacting the tissue with a therapeutically effective amount of an agent including at least one ketone ester, thereby protecting the tissue from radiation damage. Ketone esters can be used to minimize, reduce and/or prevent tissue damage following intentional and accidental radiation exposure, as well as increasing the therapeutic efficacy of radiation therapies by protecting non-target tissue from incidental radiation damage.
1. A method of protecting animal tissue from damage caused by radiation exposure, comprising contacting the tissue of a subject in need thereof with a therapeutically effective amount of an agent including at least one ketone ester, thereby protecting the tissue from radiation damage, wherein the agent is:
2. The method of claim 1 , wherein the radiation exposure is from a radioactive substance or ionizing radiation.
3. The method of claim 1 , wherein contacting is performed at least one of before, during or after exposure to radiation.
4. The method of claim 3 , wherein contacting comprises administering to the subject in need thereof the agent within two weeks prior to exposure to radiation, during radiation exposure, and/or within two weeks following radiation exposure.
5. The method of claim 3 , wherein contacting comprises administering to the subject in need thereof the agent within two weeks prior to radiation exposure.
6. The method of claim 3 , wherein contacting comprises administering to the subject in need thereof the agent within four days prior to radiation exposure, during radiation exposure, and/or within about one day following radiation exposure.
7. The method of claim 1 , wherein the radiation comprises an acute or chronic dose of ionizing or non-ionizing radiation.
8. The method of claim 7 , wherein the ionizing radiation results from nuclear fission or fusion.
9. The method of claim 7 , wherein the ionizing radiation comprises X-rays.
10. The method of claim 7 , wherein the ionizing radiation comprises radionuclides.
11. A method of enhancing the therapeutic window for radiotherapy in a subject, comprising contacting tissue of the subject with a therapeutically effective amount of an agent including at least one ketone ester prior to the radiotherapy, thereby protecting the tissue from radiation damage, wherein the agent is:
12. The method of claim 1 , wherein the radiation exposure comprises diagnostic X-rays, radiation therapy, a CAT-scan, a mammogram, a radionuclide scan, or an interventional radiological procedure under CT or fluoroscopy guidance.
13. The method of claim 1 , wherein the radiation exposure comprises tissue-incorporated radionuclides from ingestion of contaminated food or water, non-medical or unintentional exposure to ionizing radiation from a nuclear weapon, non-medical or unintentional exposure to a radioactive spill, cosmic radiation, and/or space flight-associated radiation expose.
14. The method of claim 1 , wherein the agent is administered topically, buccally, intraocularly, orally, subcutaneously, intramuscularly, intravenously, intraarterially, transdermally, intranasally, rectally, peritoneally, or by inhalation.
15. The method of claim 1 , wherein administering the compound raises the blood ketone body concentration to between 0.1 mM and 20 mM.
16. The method according to claim 15 , wherein administering the compound raises the blood ketone body concentration to between 0.2 mM and 10 mM.
17. The method according to claim 15 , wherein administering the compound raises the blood ketone body concentration to between 2 mM and 8 mM.
18. The method according to claim 14 , wherein administering comprises administering from about 5 grams to about 70 grams of the compound.
19. The method according to claim 14 , wherein administering comprises administering from about 70 milligrams to about 5 grams per kilogram of the subject's body weight.
20. The method according to claim 14 , wherein administering comprises administering from about 1 gram to about 4 grams per kilogram of the subject's body weight.
21. The method according to claim 14 , wherein administering comprises administering 130 grams to about 170 grams per day to the subject.
22. The method of claim 21 , wherein administering comprises administering 150 grams per day to the subject.