title: Bioprotective carnitinoids: lipoic acid, butyrate, and mitochondria-targeting to treat radiation injury: mitochondrial drugs come of age.
abstract: Preclinical Research Given nuclear-power-plant incidents such as the 2011 Japanese Fukushima-Daiichi disaster, an urgent need for effective medicines to protect against and treat the harmful biological effects of radiation is evident. To address such a challenge, we describe potential strategies herein including mitochondrial and epigenetic-driven methods using lipoic and butyric acid ester conjugates of carnitine. The antioxidant and other therapeutically beneficial properties of this class of agents may protect against ionizing radiation and resultant mitochondrial dysfunction. Recent studies of the compounds described herein reveal the potential-although further research and development is required to prove the effectiveness of this approach-to provide field-ready radiation-protective drugs.
authors.affiliation: PhenoMatriX, Inc., Boston, MA, USA.|Cancer Research Center, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Kosta
authors.initials: K
authors.lastname: Steliou
authors.affiliation: Cancer Research Center, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Faller
authors.affiliation: Department of Biological Sciences, College of Arts and Sciences, University of Alabama, Tuscaloosa, AL, USA.|Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Pinkert
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Irwin
authors.affiliation: SRI Biosciences, a Division of SRI International, Menlo Park, CA, USA.|Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Moos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D020148:Butyric Acid / Q000627:therapeutic use*; D002331:Carnitine; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011832:Radiation Injuries / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D056572:Histone Deacetylase Inhibitors; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D020148:Butyric Acid; D008063:Thioctic Acid; D002331:Carnitine
keywords: PMX-500; PMX-550; amyotrophic lateral sclerosis; bioterrorism; butyrate; carnitinoid; ionizing radiation; lipoic acid; mitophagy