Radiation therapy is one of the most common treatment strategies for thorax malignancies. One of the considerable limitations of this therapy is its toxicity to normal tissue. The lung is the major dose-limiting organ for radiotherapy. That is because ionizing radiation produces reactive oxygen species that induce lesions, and not only is tumor tissue damaged, but overwhelming inflammatory lung damage can occur in the alveolar epithelium and capillary endothelium. This damage may result in radiation-induced pneumonitis and/or fibrosis. While describing the lung response to irradiation generally, the main focus of this review is on cytokines and their roles and functions within the individual stages. We discuss the relationship between radiation and cytokines and their direct and indirect effects on the formation and development of radiation injuries. Although this topic has been intensively studied and discussed for years, we still do not completely understand the roles of cytokines. Experimental data on cytokine involvement are fragmented across a large number of experimental studies; hence, the need for this review of the current knowledge. Cytokines are considered not only as molecular factors involved in the signaling network in pathological processes, but also for their diagnostic potential. A concentrated effort has been made to identify the significant immune system proteins showing positive correlation between serum levels and tissue damages. Elucidating the correlations between the extent and nature of radiation-induced pulmonary injuries and the levels of one or more key cytokines that initiate and control those damages may improve the efficacy of radiotherapy in cancer treatment and ultimately the well-being of patients.
Hyaluronic acid (HA) has a special position among glycosaminoglycans. As a major component of the extracellular matrix (ECM). This simple, unbranched polysaccharide is involved in the regulation of various biological cell processes, whether under physiological conditions or in cases of cell damage. This review summarizes the history of this molecule’s study, its distinctive metabolic pathway in the body, its unique properties, and current information regarding its interaction partners. Our main goal, however, is to intensively investigate whether this relatively simple polymer may find applications in protecting against ionizing radiation (IR) or for therapy in cases of radiation-induced damage. After exposure to IR, acute and belated damage develops in each tissue depending upon the dose received and the cellular composition of a given organ. A common feature of all organ damage is a distinct change in composition and structure of the ECM. In particular, the important role of HA was shown in lung tissue and the variability of this flexible molecule in the complex mechanism of radiation-induced lung injuries. Moreover, HA is also involved in intermediating cell behavior during morphogenesis and in tissue repair during inflammation, injury, and would healing. The possibility of using the HA polymer to affect or treat radiation tissue damage may point to the missing gaps in the responsible mechanisms in the onset of this disease. Therefore, in this article, we will also focus on obtaining answers from current knowledge and the results of studies as to whether hyaluronic acid can also find application in radiation science.
Purpose: Therapeutic thorax irradiation as an intervention in lung cancer has its limitations due to toxic effects leading to pneumonitis and/or pulmonary fibrosis. It has already been confirmed that hyaluronic acid (HA), an extracellular matrix glycosaminoglycan, is involved in inflammation disorders and wound healing in lung tissue. We examined the effects after gamma irradiation of hyaluronic acid nanoparticles (HANPs) applied into lung prior to that irradiation in a dose causing radiation-induced pulmonary injuries (RIPI). Materials and Methods: Biocompatible HANPs were first used for viability assay conducted on the J774.2 cell line. For in vivo experiments, HANPs were administered intratracheally to C57Bl/6 mice 30 min before thoracic irradiation by 17 Gy. Molecular, cellular, and histopathological parameters were measured in lung and peripheral blood at days 113, 155, and 190, corresponding to periods of significant morphological and/or biochemical alterations of RIPI. Results: Modification of linear hyaluronic acid molecule into nanoparticles structure significantly affected the physiological properties and caused long-term stability against ionizing radiation. The HANPs treatments had significant effects on the expression of the cytokines and particularly on the pro-fibrotic signaling pathway in the lung tissue. The radiation fibrosis phase was altered significantly in comparison with a solely irradiated group. Conclusions: The present study provides evidence that application of HANPs caused significant changes in molecular and cellular patterns associated with RIPI. These findings suggest that HANPs could diminish detrimental radiation-induced processes in lung tissue, thereby potentially decreasing the extracellular matrix degradation leading to lung fibrosis.
We examined the effect of epidermal growth factor (EGF) treatment in mice that received bone marrow transplantation (BMT) after 11 Gy whole-body irradiation. C57Bl/6 mice were divided into three treatment groups: 0 Gy; 11 Gy ((60)Co, single dose, 0.51 Gy/min) with BMT (5 × 10(6) bone marrow cells isolated from green fluorescent protein syngeneic mice, 3-4 h postirradiation); and 11 Gy with BMT and EGF (2 mg/kg applied subcutaneously 1, 3 and 5 days postirradiation). Survival data were collected. Bone marrow, peripheral blood count and cytokines, gastrointestine and liver parameters and migration of green fluorescent protein-positive cells were evaluated at 63 days postirradiation. Epidermal growth factor increased survival of irradiated animals that received BMT from 10.7 to 85.7% at 180 days postirradiation. In the BMT group, we found changes in differential bone marrow and blood count, plasma cytokine levels, gastrointestinal tissues and liver at 63 days postirradiation. These alterations were completely or in some parameters at least partially restored by epidermal growth factor. These findings indicate that epidermal growth factor, administered 1, 3 and 5 days postirradiation in combination with bone marrow transplantation, significantly improves long-term prognosis.
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