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- W2166872103 abstract "Despite modern radiotherapy techniques, treatment of oncological patients in some cases inevitably involves irradiation of normal tissues causing undesired side effects. Exposure of oncological patients to therapeutic doses of chest irradiation has been significant source of cardiovascular morbidity and mortality. The cellular response to radiation injury initiates an active process that ultimately leads to progressive damage. This process can be modulated by therapies directed at mitigation of undesirable events resulting from injury of normal tissue.The aim of the study was to explore the effects of a single dosage radiation (25 Gy) applied to the mediastinal area of normal adult Wistar rats on the heart functional parameters and selected molecular markers 6 weeks after irradiation. Irradiation of normal tissues leads to an increase in reactive oxygen and reactive nitrogen oxide species that serve as intracellular signaling to alter cell function resulting in chronic inflammation, progressive damage, organ dysfunction, and ultimate failing of the heart.Irradiated rats exhibited general alteration reflected in decreased body mass, right ventricular hypertrophy, while left ventricle (and its function) was not affected. Morphologically, increased capillary density as well as ultrastructural signs of both, endothelial cell degeneration/regeneration, microthrombi, activated fibroblasts and monocytes were found. Gene expression of PPARα was significantly lower in left ventricular tissue of irradiated rats, while expression of microRNA-21 in these hearts was increased nearly 10-fold. Myocardial Cx43 was upregulated via reduced miRNA-1. miRNA-15b was down regulated almost 42% and Bax protein decreased, indicating triggered adaptive mechanism. Activities of circulating 72kDa MMP-2 significantly increased.It can be concluded that 6 weeks after irradiation, despite progressive deterioration of the animals and endothelial cell damage, adaptive and/or compensatory mechanisms are still working and cardiac function is maintained. On the basis of our results selected substances, which can decrease the negative impact of radiation on healthy tissue will be tested." @default.
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- W2166872103 date "2014-06-27" @default.
- W2166872103 modified "2023-09-27" @default.
- W2166872103 title "P131Mechanisms involved in early phase of cardiovascular response after mediastinal region irradiation" @default.
- W2166872103 doi "https://doi.org/10.1093/cvr/cvu082.71" @default.
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