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Mitigation of Damage from Reactive Oxygen Species and Ionizing Radiation by Ketone Body Esters 

Mitigation of Damage from Reactive Oxygen Species and Ionizing Radiation by Ketone Body Esters
Chapter:
Mitigation of Damage from Reactive Oxygen Species and Ionizing Radiation by Ketone Body Esters
Author(s):

William Curtis

, Martin Kemper

, Alexandra Miller

, Robert Pawlosky

, M. Todd King

, and Richard L. Veech

DOI:
10.1093/med/9780190497996.003.0027
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date: 06 August 2020

Reactive oxygen and nitrogen species, ROS and RNS, are ubiquitous in living cells. They have beneficial effects but are also the cause of a wide variety of diseases. However adding excessive amounts of reducing agents has a long history of clinical failure. This problem can be overcome by providing a novel ester of D-beta-hydroxybutyrate–R-1,3-butanediol, which is rapidly hydrolyzed to ketone bodies, the metabolism of which leads to the production of NADPH. The free cytosolic [NADP+]/[NADPH] redox potential is the most negative in the cell and sets the potential of the glutathione and ascorbic acid couples. Ketone bodies also act by inhibiting histone deacetylases, activating the transcription factor FOXO3 and increasing the transcription of enzymes involved in the destruction of ROS. Ketone esters would be effective in the treatment of a variety of disparate diseases where ROS play a role, ranging from Parkinson’s disease to radiation sickness and aging.

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