Abstract
The aim of the study was to investigate long-term effects of radiation on the (ultra)structure and function of the liver in mice. The experiments were conducted on wild-type C57BL/6J and apolipoprotein E knock-out (ApoE−/−) male mice which received a single dose (2 or 8 Gy) of X-rays to the heart with simultaneous exposure of liver to low doses (no more than 30 and 120 mGy, respectively). Livers were collected for analysis 60 weeks after irradiation and used for morphological, ultrastructural, and biochemical studies. The results show increased damage to mitochondrial ultrastructure and lipid deposition in hepatocytes of irradiated animals as compared to non-irradiated controls. Stronger radiation-related effects were noted in ApoE−/− mice than wild-type animals. In contrast, radiation-related changes in the activity of lysosomal hydrolases, including acid phosphatase, β-glucuronidase, N-acetyl-β-d-hexosaminidase, β-galactosidase, and α-glucosidase, were observed in wild type but not in ApoE-deficient mice, which together with ultrastructural picture suggests a higher activity of autophagy in ApoE-proficient animals. Irradiation caused a reduction of plasma markers of liver damage in wild-type mice, while an increased level of hepatic lipase was observed in plasma of ApoE-deficient mice, which collectively indicates a higher resistance of hepatocytes from ApoE-proficient animals to radiation-mediated damage. In conclusion, liver dysfunctions were observed as late effects of irradiation with an apparent association with malfunction of lipid metabolism.
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Acknowledgements
The research received funding from the European Atomic Energy Community’s Seventh Framework Programme (FP7/2007–2011) under the grant agreement no. 211403 (CARDIORISK) and from the National Science Center, Poland under the grant no. N-402685640. We thank Dr Marta Gawin for critical reading of the manuscript. We also acknowledge the contribution of Hermann Fuchs, PhD, regarding estimation of the dose to the liver.
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411_2018_734_MOESM1_ESM.jpg
Distribution of radiation dose. Intensity and space distribution of a dose (A and B), and a shape of irradiated mouse (C). Heart area and liver area are marked with red and blue, respectively, on the radiography picture; the arrowhead points the liver are used for experiments (JPG 68 KB)
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Lysek-Gladysinska, M., Wieczorek, A., Walaszczyk, A. et al. Long-term effects of low-dose mouse liver irradiation involve ultrastructural and biochemical changes in hepatocytes that depend on lipid metabolism. Radiat Environ Biophys 57, 123–132 (2018). https://doi.org/10.1007/s00411-018-0734-9
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DOI: https://doi.org/10.1007/s00411-018-0734-9