Original ArticlePlasma metabolite biomarkers predictive of radiation induced cardiotoxicity
Section snippets
Animal irradiation and sample collection
Rat local heart irradiation was performed as described previously [9]. In short, male SD rats were obtained from Charles River Laboratories and maintained on a 12:12 light-to-dark cycle with free access to food and water. At a weight of 250–290 g (about 9 weeks of age), rats received local heart irradiation using an image-guided X-ray machine (Small Animal Conformal RT Device, SACRTD). Rats were anesthetized with 3% isoflurane and placed vertically in a cylindrical Plexiglas holder that was cut
Results
Exposure to ionizing radiation causes long-term changes in metabolic profiles of rat heart and plasma. We have previously reported on radiation-induced alterations in mitochondria in the heart of adult male SD rats, either after a single dose of X-rays to the heart [5] or after five once-a-day fractions of 9 Gy (5 × 9 Gy) [9]. At 6 months after 5 × 9 Gy local heart irradiation, small but statistically significant changes in cardiac function and a small increase in cardiac collagen deposition
Discussion
Exposure of the heart to radiation leads to significant morbidity and mortality in survivors of cancer. The risk of cardiac events increases in a dose-dependent manner [21]. Elevated risk begins within the first few years and continues for decades after RT [22]. Current practices for diagnosis and prediction of patients at risk for RT related cardiac events are not yet developed. Commonly available testing such as echocardiogram and nuclear medicine studies are not used routinely and do not
Acknowledgments
This work was supported by CCSG Developmental funding LCCC-AWD413088, Georgetown University, Washington DC, United States to KU and AKC and 1U01AI133561-01 funding from, National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID), Bethesda, Maryland, United States to MB and AKC. The authors would like to acknowledge the Metabolomics Shared Resource in Georgetown University (Washington, DC, USA) which is partially supported by NIH/NCI/CCSG grant P30-CA051008,
Author contributions
Study design: KU, MBS, AKC. Performance of the study: CY, AB, EAB, VS. Metabolomic Data acquisition and analysis: MJ, YL, MG. Drafting of the manuscript: AKC, KU, YL, MBS. All authors have read and approved the final version of the submitted manuscript.
Competing interests
The author(s) declare no competing interests.
Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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