Radiation-induced lung injury

About: Radiation-induced lung injury is a research topic. Over the lifetime, 258 publications have been published within this topic receiving 6877 citations. The topic is also known as: Radiation Pneumonitis.

Changes in Expression of Injury After Irradiation of Increasing Volumes in Rat Lung

Abstract: Purpose: To improve the cure rates of thoracic malignancies by radiation dose escalation, very accurate insight is required in the dose delivery parameters that maximally spare normal lung function. Radiation-induced lung complications are classically divided into an early pneumonitic and a late fibrotic phase. This study investigated the relative dose–volume sensitivity, underlying pathologic findings, and consequentiality of early to late pathologic features. Methods and Materials: We used high-precision, graded dose–volume lung irradiations and followed the time dependency of the morphologic sequelae in relation to overall respiratory function. Results: Two distinct pathologic lesions were identified in the early postirradiation period (6–12 weeks): vascular inflammation and parenchymal inflammation. Vascular inflammation occurred at single doses as low as 9 Gy. This translated into early respiratory dysfunction only when a large lung volume had been irradiated and was reversible with time. Parenchymal inflammation was seen after higher doses only (onset at 16 Gy), progressed into later fibrotic remodeling but did not translate into dysfunction at a 25% lung volume even after single doses up to 36 Gy. Conclusion: Our data imply that a low dose scattered over a large lung volume causes more early toxicity than an extreme dose confined to a small volume. Such findings are crucial for clinical treatment planning of dose escalations and choices for modern radiotherapy techniques.

Polydatin alleviated radiation‐induced lung injury through activation of Sirt3 and inhibition of epithelial–mesenchymal transition

Abstract: Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. It is characterized with two main features including early radiation pneumonitis and fibrosis in later phase. This study was to investigate the potential radioprotective effects of polydatin (PD), which was shown to exert anti-inflammation and anti-oxidative capacities in other diseases. In this study, we demonstrated that PD-mitigated acute inflammation and late fibrosis caused by irradiation. PD treatment inhibited TGF-β1-Smad3 signalling pathway and epithelial-mesenchymal transition. Moreover, radiation-induced imbalance of Th1/Th2 was also alleviated by PD treatment. Besides its free radical scavenging capacity, PD induced a huge increase of Sirt3 in culture cells and lung tissues. The level of Nrf2 and PGC1α in lung tissues was also elevated. In conclusion, our data showed that PD attenuated radiation-induced lung injury through inhibiting epithelial-mesenchymal transition and increased the expression of Sirt3, suggesting PD as a novel potential radioprotector for RILI.

Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability.

Abstract: Background/Aims: Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage. However, unlike other injuries, RILI received limited therapeutic effects from implanted MSCs due to local hypoxia and extensive reactive oxygen species (ROS) in irradiated lungs. Since the poor survival of MSCs is primarily due to hypoxia and ROS generation, we hypothesize that persistent and adaptive hypoxia treatment induces enhanced resistance to hypoxic stress in implanted MSC. The aim of this study is to investigate whether persistent and adaptive hypoxia treatment of bmMSCs prior to their transplantation in injured mice enhanced survival and improved curative effects in RILI. Methods: Primary bmMSCs were obtained from the marrow of six-week-old male C57BL6/J mice and were cultured either under normoxic conditions (21% O 2 ) or hypoxic conditions (2.5% O 2 ). Mice were injected with normoxia/hypoxia MSCs after thoracic irradiation (20 Gy). The therapeutic effects of MSCs on RILI were assessed by pathological examinations that included HE meanwhile, inflammatory factors were measured using an ELISA. The morphology of MSCs in vitro was recorded using a microscope and identified by flow cytometry, cell viability was measured using the CCK-8 assay, the potential for proliferation was detected by the EdU assay, and ROS levels were measured using a ROS fluorogenic probe. In addition, HIF-1α and several survival pathway proteins (Akt, p-Akt, Caspase-3) were also detected by western blotting. Results: Implanted MSCs alleviated both early radiation-induced pneumonia and late pulmonary fibrosis. However, hypoxia MSCs displayed a more pronounced therapeutic effect compared to normoxia MSCs. Compared to normoxia MSCs, the hypoxia MSCs demonstrated greater cell viability, an enhanced proliferation potential, decreased ROS levels and increased resistance to hypoxia and ROS stress. In addition, hypoxia MSCs achieved higher activation levels of HIF-1α and Akt, and HIF-1α played a critical role in the development of resistance. Conclusion: Hypoxia enhances the therapeutic effect of mesenchymal stromal cells on radiation-induced lung injury by promoting MSC proliferation and improving their antioxidant ability, mediated by HIF-1α.

Melatonin reduces X-ray radiation-induced lung injury in mice by modulating oxidative stress and cytokine expression.

Abstract: Purpose: The modification of radiation-induced lung injuries by melatonin was studied by measuring changes in oxidative stress, cytokine expression and histopathology in the lung tissue of mice following irradiation.Materials and methods: The thoraces of C57BL/6 mice were exposed to a single X-ray radiation dose of 12 Gy with or without 200 mg/kg of melatonin pretreatment. The level and localization of transforming growth factor (TGF)-β1 protein were measured using an enzyme-linked immunosorbent assay (ELISA) method and immunohistochemical staining, respectively. Real-time quantitative polymerase chain reaction (PCR) was established to evaluate the relative mRNA expression levels of TGF-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6.Results: Malondialdehyde (MDA) levels increased after irradiation and then significantly reduced (1.9-fold) under melatonin treatment. Changes in superoxide dismutase (SOD) and catalase activities, as well as glutathione (GSH) levels, after irradiation...