title: Effects of late administration of pentoxifylline and tocotrienols in an image-guided rat model of localized heart irradiation.
abstract: Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation.
authors.affiliation: Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Sridharan
authors.forename: Preeti
authors.initials: P
authors.lastname: Tripathi
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
authors.forename: Peter M
authors.initials: PM
authors.lastname: Corry
authors.forename: Eduardo G
authors.initials: EG
authors.lastname: Moros
authors.forename: Awantika
authors.initials: A
authors.lastname: Singh
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Compadre
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002452:Cell Count; D004347:Drug Interactions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D023421:Models, Animal; D058958:Organs at Risk / Q000528:radiation effects; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011832:Radiation Injuries / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D024508:Tocotrienols / Q000008:administration & dosage* / Q000494:pharmacology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010431:Pentoxifylline; D051571:Protein Kinase C-alpha; D051057:Proto-Oncogene Proteins c-akt; D011837:Radiation-Protective Agents; D024508:Tocotrienols; C067980:CD68 antigen, human; D000097382:CD68 Molecule
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