title: A tocotrienol-enriched formulation protects against radiation-induced changes in cardiac mitochondria without modifying late cardiac function or structure.
abstract: Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or 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.forename: Preeti
authors.initials: P
authors.lastname: Tripathi
authors.forename: Nukhet
authors.initials: N
authors.lastname: Aykin-Burns
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Krager
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Eduardo G
authors.initials: EG
authors.lastname: Moros
authors.forename: Stepan B
authors.initials: SB
authors.lastname: Melnyk
authors.forename: Oleksandra
authors.initials: O
authors.lastname: Pavliv
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
mesh_terms: D000818:Animals; D019069:Cell Respiration / Q000187:drug effects / Q000528:radiation effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology / Q000528:radiation effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000473:pathology; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D024508:Tocotrienols / Q000008:administration & dosage*; D014965:X-Rays
chemical_list: D011837:Radiation-Protective Agents; D024508:Tocotrienols