title: Late Administration of a Palladium Lipoic Acid Complex (POLY-MVA) Modifies Cardiac Mitochondria but Not Functional or Structural Manifestations of Radiation-Induced Heart Disease in a Rat Model.
abstract: Exposure of the heart to ionizing radiation can cause adverse myocardial remodeling. In small animal models, local heart irradiation causes persistent alterations in cardiac mitochondrial function and swelling. POLY-MVA is a dietary supplement that contains a palladium lipoic acid complex that targets mitochondrial complex I and has been demonstrated to have greater redox potential than lipoic acid alone. POLY-MVA improves mitochondrial function and anti-oxidant enzyme activity in the aged rat heart. In this study, we tested whether POLY-MVA can mitigate cardiac effects of ionizing radiation. Adult male rats were exposed to local heart X rays with a daily dose of 9 Gy for 5 consecutive days. Eighteen weeks after irradiation, POLY-MVA was administered orally at 1 ml/kg bodyweight per day during weekdays, for 6 weeks. Alterations in cardiac function as measured with echocardiography coincided with enhanced mitochondrial swelling, a reduction in mitochondrial expression of complex II, manifestations of adverse remodeling such as a reduction in myocardial microvessel density and an increase in collagen deposition and mast cell numbers. POLY-MVA enhanced left ventricular expression of superoxide dismutase 2, but only in sham-irradiated animals. In irradiated animals, POLY-MVA caused a reduction in markers of inflammatory infiltration, CD2 and CD68. Moreover, POLY-MVA mitigated the effects of radiation on mitochondria. Nonetheless, POLY-MVA did not mitigate adverse cardiac remodeling, suggesting that this tissue remodeling may not be alleviated by altering cardiac mitochondria alone. However, we cannot exclude the possibility that an earlier onset of POLY-MVA administration may have more profound effects on radiation-induced cardiac remodeling.
authors.affiliation: a   University of Arkansas for Medical Sciences, Department of Pharmaceutical Sciences, Division of Radiation Health, Little Rock, Arkansas.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Sridharan
authors.affiliation: a   University of Arkansas for Medical Sciences, Department of Pharmaceutical Sciences, Division of Radiation Health, Little Rock, Arkansas.
authors.forename: John W
authors.initials: JW
authors.lastname: Seawright
authors.affiliation: b   Garnett McKeen Laboratory, Inc., Bohemia, New York.|c   St. Joseph's College, Patchogue, New York.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Antonawich
authors.affiliation: b   Garnett McKeen Laboratory, Inc., Bohemia, New York.
authors.forename: Merrill
authors.initials: M
authors.lastname: Garnett
authors.affiliation: a   University of Arkansas for Medical Sciences, Department of Pharmaceutical Sciences, Division of Radiation Health, Little Rock, Arkansas.
authors.forename: Maohua
authors.initials: M
authors.lastname: Cao
authors.affiliation: a   University of Arkansas for Medical Sciences, Department of Pharmaceutical Sciences, Division of Radiation Health, Little Rock, Arkansas.
authors.forename: Preeti
authors.initials: P
authors.lastname: Singh
authors.affiliation: a   University of Arkansas for Medical Sciences, Department of Pharmaceutical Sciences, Division of Radiation Health, Little Rock, Arkansas.
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D011832:Radiation Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000737:chemistry*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018801:CD2 Antigens; D009942:Organometallic Compounds; D010165:Palladium; D008063:Thioctic Acid; C067980:CD68 antigen, human; D000097382:CD68 Molecule