Purpose: Insulin-like growth factor-1 (IGF-1) stimulates epithelial regeneration but may also induce life-threatening hypoglycemia. In our study, we first assessed its safety. Subsequently, we examined the effect of IGF-1 administered in different dose regimens on gastrointestinal damage induced by high doses of gamma radiation. Material and methods: First, fasting C57BL/6 mice were injected subcutaneously with IGF-1 at a single dose of 0, 0.2, 1, and 2 mg/kg to determine the maximum tolerated dose (MTD). The glycemic effect of MTD (1 mg/kg) was additionally tested in non-fasting animals. Subsequently, a survival experiment was performed. Animals were irradiated (60Co; 14, 14.5, or 15 Gy; shielded head), and IGF-1 was administered subcutaneously at 1 mg/kg 1, 24, and 48 h after irradiation. Simultaneously, mice were irradiated (60Co; 12, 14, or 15 Gy; shielded head), and IGF-1 was administered subcutaneously under the same regimen. Jejunum and lung damage were assessed 84 h after irradiation. Finally, we evaluated the effect of six different IGF-1 dosage regimens administered subcutaneously on gastrointestinal damage and peripheral blood changes in mice 6 days after irradiation (60Co; 12 and 14 Gy; shielded head). The regimens differed in the number of doses (one to five doses) and the onset of administration (starting at 1 [five regimens] or 24 h [one regimen] after irradiation). Results: MTD was established at 1 mg/kg. MTD mitigated lethality induced by 14 Gy and reduced jejunum and lung damage caused by 12 and 14 Gy. However, different dosing regimens showed different efficacy, with three and four doses (administered 1, 24, and 48 h and 1, 24, 48, and 72 h after irradiation, respectively) being the most effective. The three-dose regimens supported intestinal regeneration even if the administration started at 24 h after irradiation, but its potency decreased. Conclusion: IGF-1 seems promising in the mitigation of high-dose irradiation damage. However, the selected dosage regimen affects its efficacy.

• Klíčová slova
• blood, insuline-like growth factor- 1, intestine, ionizing radiation, lung, mice,
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• hyaluronan receptor, hyaluronic acid, radiation, radioprotection, therapeutic application,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

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.

• Klíčová slova
• hyaluronic acid, lung, nanoparticles, radiation, radiation fibrosis,
• Publikační typ
• časopisecké články MeSH