Abstract:Injury-induced by ionizing radiation (IR) severely reduces the quality of life of victims. The development of radiation protectors is regarded as one of the most resultful strategies to alleviate damages caused by IR exposure. In the present study, we investigated the radioprotective effects of the agonist of nucleotide-binding-oligomerization-domaincontaining proteins 2 called murabutide (MBD) and clarified the potential mechanisms.Our results showed that the pretreatment with MBD effectively protected cultur… Show more
“…Furthermore, an increase in oxidative stress and a decrease in cell viability was observed after low-dose radiation exposure as well. Therefore, low-dose radiation exposure does not only act as an alarmin but also mediates oxidative stress, similar to what was observed in previous studies conducted on relatively high-dose radiation exposures 26 . Subsequently, HMGB1 levels can be lowered and oxidative stress reduced with GL, a direct inhibitor of HMGB1, that subsequently might allow the preservation of cell viability.…”
Glycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.
“…Furthermore, an increase in oxidative stress and a decrease in cell viability was observed after low-dose radiation exposure as well. Therefore, low-dose radiation exposure does not only act as an alarmin but also mediates oxidative stress, similar to what was observed in previous studies conducted on relatively high-dose radiation exposures 26 . Subsequently, HMGB1 levels can be lowered and oxidative stress reduced with GL, a direct inhibitor of HMGB1, that subsequently might allow the preservation of cell viability.…”
Glycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.
“…Furthermore, it must be noted that this preliminary study presented here, lacks an exploration of other important factors that mediate radiation enteritis, such as the destruction of the intestinal epithelial barrier and tight junction after irradiation exposure [12,44]. Besides, irradiation exposure not only acts as a proinflammatory signal [5,45], but also mediates oxidative and nitrative stress to induce the production of ROS and NOS in the small intestine [7,9,46,47]. In addition, GL has been reported to possess anti-oxidant properties in a recent study [48].…”
Section: Discussionmentioning
confidence: 96%
“…e small intestine is considered to be one of the most sensitive tissues in the abdomen to radiation exposure. After transient radiation exposure, ROS and NOS are immediately generated [5][6][7], which can cause severe cell damage, including DNA damage and the release of intracellular cytokines [8,9]. Radiation-induced DNA damage can act as a damage-associated molecular pattern (DAMP) to stimulate inflammatory responses, as well as destruction of the intestinal epithelial barrier mediated by abdominal radiation exposure, ultimately resulting in radiation enteritis [5,[9][10][11].…”
Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients’ tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.
“…At the same time, NOD2 alleviates radiation-induced damage through the agonist of ATR-mediated DNA damage response pathway, Morabutanol, and also inhibits oxidative stress and apoptosis by blocking the participation of wow/ROCK-mediated TAK1/ NOD2 in NF-κB pathway. 28 - 30 Meanwhile, NOD2 also plays an important role in Parkinson’s disease and intestinal disease. 31 , 32 Interferon regulatory factor 7 (IRF7) is highly expressed in the apoptosis of melanoma cell after ultraviolet irradiation, and it is used as a reactive molecular indicator of radiation-induced injury of human umbilical vein endothelial cells.…”
The health of radiation workers has always been our focus. Epidemiological investigation shows that long-term exposure to low-dose ionizing radiation can affect human health, especially cancer and cardiovascular disease, and there are many studies on it. However, up to now, there have been few reports on the research of blood and biological samples from radiation workers. In this study, radiation workers and healthy control groups were strictly screened, and the transcriptome of mRNA and circRNA was sequenced by extracting their peripheral venous blood. At the same time, appropriate data sets were selected in the GEO database for bioinformatics analysis, and circRNA-miRNA-mRNA network was constructed. We identified 9 different circular ribonucleic acids, 3 tiny ribonucleic acids, and 2 central genes (NOD 2 and IRF 7). These differentially expressed genes and non-coding RNA are closely related to ionizing radiation damage, and play an important role as biological markers. In conclusion, this study may provide new insights into the role of the circRNA-miRNA-mRNA regulatory network in the health of radiation workers, and provides a new strategy for the future study of radiation biology.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.