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Title: Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat

Abstract

During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD andmore » glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab.« less

Authors:
; ;  [1]
  1. Facultes de Medecine et de Pharmacie, Dijon (France) [and others
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
160185
Resource Type:
Journal Article
Resource Relation:
Journal Name: Radiation Research; Journal Volume: 144; Journal Issue: 1; Other Information: PBD: Oct 1995
Country of Publication:
United States
Language:
English
Subject:
56 BIOLOGY AND MEDICINE, APPLIED STUDIES; 55 BIOLOGY AND MEDICINE, BASIC STUDIES; HEART; BIOLOGICAL RADIATION EFFECTS; BIOCHEMICAL REACTION KINETICS; X RADIATION; DOSE RATES; CHEST; RADIOTHERAPY; IRRADIATION; RATS; VITAMIN E; ANTIOXIDANTS

Citation Formats

Benderitter, M., Assem, M., and Maupoil, V. Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat. United States: N. p., 1995. Web. doi:10.2307/3579237.
Benderitter, M., Assem, M., & Maupoil, V. Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat. United States. doi:10.2307/3579237.
Benderitter, M., Assem, M., and Maupoil, V. 1995. "Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat". United States. doi:10.2307/3579237.
@article{osti_160185,
title = {Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat},
author = {Benderitter, M. and Assem, M. and Maupoil, V.},
abstractNote = {During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab.},
doi = {10.2307/3579237},
journal = {Radiation Research},
number = 1,
volume = 144,
place = {United States},
year = 1995,
month =
}
  • Coronary sinus catheterization was performed in 13 dogs. Following an irradiation of 4,000 r to the heart, the A-V difference of glucose in the coronary sinus was decreased; pyruvic and lactic acids and creatine were temporarily increased. Following irradiation of 1,000 to 4,000 r to the hearts of 28 rabbits, the glycogen in the heart muscle decreased, while the glucose, pyruvic and lactic acids, creatine and creatinine contents temporarily increased. In irradiated dogs and rabbits, the porphyrin affinity of the heart muscle was diminished. In 6 toads, no change was found in the lactic dehydrogenase activity even after 6925 rmore » irradiation to the heart. The disturbance of glucose metabolism in the irradiated heart muscle appears to be not in the anaerobic processes but in the aerobic phase, especially in the electron transport system in the mitochondria. (auth)« less
  • Electrocardiograms were obtained on 52 normal dogs before and after cardiac irradiation with 1,300, 2,000, and 2,500 r. No ectopic cardiac arrhythmias were noted on electrocardiograms obtained 7 to 90 days following the completion of the course of irradiation. A mean increase in the ventricular rate was noted 7 days following the completion of the course of irradiation, but was not present 30 to 60 days later. There was no prolongation of PR interval or QRS duration following cardiac irradiation. At the dosage levels employed, irradiation of the normal canine heart produced no electrocardiographic changes indicative of gross myocardial damage.more » This was noted to be true as long as 90 days following the completion of the course of irradiation. (auth)« less
  • In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 {mu}M) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP{sup +}, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of themore » system was further evaluated by measuring the rate of evolution of {sup 14}CO{sub 2} from D-({sup 14}C(U))-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.« less
  • Pulmonary antioxidants and their therapeutic implications have been extensively studied during past decades. The purpose of this review is to briefly summarize the key findings of these studies as well as to elaborate on some novel approaches with respect to potential preventive treatments for neonatal chronic lung disease bronchopulmonary dysplasia (BPD). Such new ideas include, for example, modification of transcription factors governing the hypoxic response pathways, important in angiogenesis, cell survival, and glycolytic responses. The fundamental strategy behind that approach is that fetal lung normally develops under hypoxic conditions and that this hypoxic, growth-favoring environment is interrupted by a prematuremore » birth. Importantly, during fetal lung development, alveolar development appears to be dependent on vascular development. Therefore, enhancement of signaling factors that occur during hypoxic fetal life ('continued fetal life ex utero'), including angiogenic responses, could potentially lead to improved lung growth and thereby alleviate the alveolar and vascular hypoplasia characteristic of BPD.« less
  • An efficient handling of superoxides by antioxidant defenses is a crucial issue for cells with respiratory chain deficient mitochondria. We used human cultured skin fibroblasts to delineate the mechanism controlling the expression of antioxidant defenses in the case of a severe ATPase deficiency resulting from an 8993T>G mutation in the mitochondrial ATPase6 gene. We observed the nuclear translocation of the transcription factor Nrf2 associated with thinning of the actin stress fibers. The mobilization of the Nrf2 signaling pathway could be mimicked by a chemical blockade of the ATPase with a specific inhibitor, oligomycin. Interestingly enough, Nrf2 nuclear translocation was notmore » observed in the case of a severe cytochrome oxidase deficiency, indicating that studying the status of this signaling pathway could throw some light on the importance of the oxidative insult associated with different respiratory chain defects.« less