Metabolic changes in mice cardiac tissue after low-dose irradiation revealed by 1H NMR spectroscopy.

Mateusz Ciszek,ᴌukasz Boguszewicz,Dorota Gabryś,Roland Kulik,Maria Sokół,Michalina Gramatyka

doi:10.1093/jrr/rrz079

Mateusz Ciszek, ᴌukasz Boguszewicz + Show 4 more

Open Access

https://doi.org/10.1093/jrr/rrz079

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Abstract

Ionizing radiation may cause cardiotoxicity not only at high, but even at low (considered as harmless) doses, yet the molecular mechanisms of the heart’s response to low doses are not clear. In this work, we used high-resolution nuclear magnetic resonance (NMR) spectroscopy to detect the early and late effects of radiation on the metabolism of murine hearts. The hearts of C57Bl/6NCrl female mice were irradiated in vivo with single 0.2 Gy or 2 Gy doses using 6 MV photons, then tissues were collected 48 h and 20 weeks after exposure. The most distinct changes in the profile of polar metabolites were detected 48 h after irradiation with 2 Gy, and included increased levels of pantothenate and glutamate as well as decreased levels of alanine, malonate, acetylcarnitine, glycine and adenosine. Significant effects of the 2 Gy dose were also observed 20 weeks after irradiation and included decreased levels of glutamine and acetylcarnitine when compared with age-matched controls. Moreover, several differences were observed between hearts irradiated with 2 Gy and analyzed either 48 h or 20 weeks after the exposure, which included changes in levels of acetylcarnitine, alanine, glycine, glutamate, glutamine, formate, myo-inositol and trimethylamine. No statistically significant effects induced by the 0.2 Gy dose were observed 20 weeks after irradiation. In general, radiation-affected compounds were associated with energy metabolism, fatty acid beta-oxidation, oxidative stress and damage to cell structures. At the same time, radiation-related effects were not detected at the level of tissue histology, which indicated a higher sensitivity of metabolomics-based tests for cardiac tissue response to radiation.

Highlights

Ionizing radiation can damage all types of cells, but the radiosensitivity of actively dividing cells is much higher than that of cells that are neither meiotically nor mitotically active
Significant effects of the 2 Gy dose were observed 20 weeks after irradiation and included decreased levels of glutamine and acetylcarnitine when compared with age-matched controls
We have previously shown that exposure of cardiomyocytes in vitro to a relatively low dose of radiation (2 Gy) that does not affect cell viability, markedly affects their metabolic profiles

Summary

Introduction

Ionizing radiation can damage all types of cells, but the radiosensitivity of actively dividing cells is much higher than that of cells that are neither meiotically nor mitotically active. It is known that a single exposure to a high dose of radiation (>15 Gy) delivered to the heart exerts an adverse long-term effect on cardiovascular functions. It results in morphological degeneration, mechanical dysfunction, damage to the endothelium and increased mortality. Such radiation-induced cardiac injuries are suggested to be mediated by a micro-vascular injury caused by inflammation and oxidative stress [2]. A number of studies have suggested that the biological and molecular response to very low doses and dose rates of ionizing radiation may differ from that of high doses [3]. Very low doses (0.025–0.05 Gy), given at a low dose rate, were shown to be protective [5]

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