scholarly journals Protective Effects of Myrtol Standardized Against Radiation-Induced Lung Injury

2016 ◽  
Vol 38 (2) ◽  
pp. 619-634 ◽  
Author(s):  
De-yun Zhao ◽  
Hong-jin Qu ◽  
Jia-ming Guo ◽  
Hai-nan Zhao ◽  
Yan-yong Yang ◽  
...  
Keyword(s):  
Single Dose ◽  
Lung Injury ◽  
Major Complication ◽  
The Body ◽  
Protective Effects ◽  
Western Blot Assay ◽  
Tnf Α ◽  
Radiation Induced ◽  
The Impact ◽  
Tgf Β1

Background/Aims: As a major complication after thoracic radiotherapy, radiation-induced lung injury (RILI) has great impact on long term quality of life and could result in fatal respiratory insufficiency The present study was aimed to evaluate the effects of Myrtol standardized on RILI, and to investigate the underlying mechanism. Methods: A mouse model of radiation-induced lung injury was generated by using thoracic irradiation with a single dose of 16Gy. Mice were orally administrated with Myrtol (25 mg/kg/day) for 4 weeks after irradiation, while prednisone (5 mg/kg/day) was used as a positive control. After then, the body weight and lung coefficient were calculated. The severity of fibrosis was evaluated by observing pulmonary sections after radiation and collagen content in lung tissues was calculated following the hydroxyproline (HYP) assay. Pathological changes were observed in all the groups by using HE staining and Masson staining. The serum levels of TGF-β1, TNF-α, IL-1β, IL-6, and PGE2 were also measured with an ELISA assay. Western blot assay was used to measure the impact of Myrtol on AKT and its downstream signaling pathway, including MMP-2 and MMP-9. The levels of Vimentin and α-SMA were evaluated with an immunofluorescence assay. Results: Treatment with Myrtol standardized, but not prednisone, reduced lung coefficient and collagen deposition in lung tissues, while attenuated histological damages induced by irradiation. Myrtol standardized also reduced the production of MDA, while increased the level of SOD. It was also observed that Myrtol standardized inhibited TGF-β1 and a series of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, PGE2. While in prednisone group, even though the early pneumonitis was ameliorated, the collagen disposition remained unchanged in latter times. Immunofluorescence analysis also revealed elevation of vimentin and α-SMA in the alveoli after a single dose of 16Gy. Conclusion: The present results suggest Myrtol standardized as an effective agent for attenuating the lung injury induced by irradiation.

scholarly journals Protective effects of ulinastatin and methylprednisolone against radiation-induced lung injury in mice

2016 ◽  
Vol 57 (5) ◽  
pp. 505-511 ◽  
Author(s):  
Yu Sun ◽  
Yu-Jun Du ◽  
Hui Zhao ◽  
Guo-Xing Zhang ◽  
Ni Sun ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Transforming Growth Factor ◽  
Lavage Fluid ◽  
Protective Effects ◽  
Pathological Changes ◽  
Tnf Α ◽  
Methylprednisolone Treatment ◽  
Radiation Induced ◽  
Tgf Β1

Abstract The effectiveness of ulinastatin and methylprednisolone in treating pathological changes in mice with radiation-induced lung injury (RILI) was evaluated. Forty C57BL/6 female mice received whole-chest radiation (1.5 Gy/min for 12 min) and were randomly allocated into Group R (single radiation, n =  10), Group U (ulinastatin treatment, n =  10), Group M (methylprednisolone treatment, n =  10), or Group UM (ulinastatin and methylprednisolone treatment, n =  10). Another 10 untreated mice served as controls (Group C). Pathological changes in lung tissue, pulmonary interstitial area density (PIAD) and expression levels of transforming growth factor β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in lung tissue, serum and bronchoalveolar lavage fluid were determined. Alleviation of pathological changes in lung tissue was observed in Groups U, M and UM. Treatment with ulinastatin, methylprednisolone or both effectively delayed the development of fibrosis at 12 weeks after radiation. Ulinastatin, methylprednisolone or both could alleviate the radiation-induced increase in the PIAD ( P  < 0.05 or P  < 0.01). Treatment with ulinastatin, methylprednisolone or both significantly reduced the expression of TNF-α, but not TGF-β1, at 9 weeks after radiation compared with Group R ( P  < 0.01). Ulinastatin and / or methylprednisolone effectively decreased the level of TNF-α in lung tissue after RILI and inhibited both the inflammatory response and the development of fibrosis.

scholarly journals Potential role of senescent macrophages in radiation-induced pulmonary fibrosis

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Lulu Su ◽  
Yinping Dong ◽  
Yueying Wang ◽  
Yuquan Wang ◽  
Bowen Guan ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Pulmonary Fibrosis ◽  
Late Toxicity ◽  
Airway Epithelial ◽  
Tnf Α ◽  
Elevated Expression ◽  
Radiation Induced ◽  
Therapeutic Radiation ◽  
Tgf Β1

AbstractRadiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results have shown that senescent cells, such as fibroblast and type II airway epithelial cell, are strongly implicated in pathology of RIPF. However, the role of senescent macrophages in the development RIPF is still unknown. In this study, we report that ionizing radiation (IR) increase cellular senescence with higher expression of senescence-associated β-galactosidase (SA-β-Gal) and senescence-specific genes (p16, p21, Bcl-2, and Bcl-xl) in irradiated bone marrow-derived monocytes/macrophages (BMMs). Besides, there’s a significant increase in the expression of pro-fibrogenic factors (TGF-β1 and Arg-1), senescence-associated secretory phenotype (SASP) proinflammatory factors (Il-1α, Il-6, and Tnf-α), SASP chemokines (Ccl2, Cxcl10, and Ccl17), and SASP matrix metalloproteinases (Mmp2, Mmp9 and Mmp12) in BMMs exposed to 10 Gy IR. In addition, the percentages of SA-β-Gal+ senescent macrophages are significantly increased in the macrophages of murine irradiated lung tissue. Moreover, robustly elevated expression of p16, SASP chemokines (Ccl2, Cxcl10, and Ccl17) and SASP matrix metalloproteinases (Mmp2, Mmp9, and Mmp12) is observed in the macrophages of irradiated lung, which might stimulate a fibrotic phenotype in pulmonary fibroblasts. In summary, irradiation can induce macrophage senescence, and increase the secretion of SASP in senescent macrophages. Our findings provide important evidence that senescent macrophages might be the target for prevention and treatment of RIPF.

Protective effects of hydrogen against irradiation

2021 ◽  
Vol 27 ◽  
Author(s):  
Yasuhiro Terasaki ◽  
Mika Terasaki ◽  
Akira Shimizu
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Cultured Cells ◽  
Animal Experiments ◽  
Lung Epithelial Cells ◽  
Lung Damage ◽  
Protective Effects ◽  
Chronic Radiation ◽  
Radiation Induced ◽  
Reactive Oxidants

: Radiation-induced lung injury is characterized by an acute pneumonia phase followed by a fibrotic phase. At the time of irradiation, a rapid, short-lived burst of reactive oxygen species (ROS) such as hydroxyl radicals (•OH) occurs, but chronic radiation-induced lung injury may occur due to excess ROS such as H2O2 , O2•− , ONOO− , and •OH. Molecular hydrogen (H2 ) is an efficient antioxidant that quickly diffuses cell membranes, reduces ROS such as •OH and ONOO− , and suppresses damage caused by oxidative stress in various organs. In 2011, through the evaluation of electron-spin resonance and fluorescent indicator signals, we had reported that H2 can eliminate •OH and can protect against oxidative stress-related apoptotic damage induced by irradiation of cultured lung epithelial cells. We had explored for the first time the radioprotective effects of H2 treatment on acute and chronic radiation-induced lung damage in mice by inhaled H2 gas (for acute) and imbibed H2 -enriched water (for chronic). Thus, we had proposed that H2 be considered a potential radioprotective agent. Recent publications have shown that H2 directly neutralizes highly reactive oxidants and indirectly reduces oxidative stress by regulating the expression of various genes. By regulating gene expression, H2 functions as an anti-inflammatory and anti-apoptotic molecule and promotes energy metabolism. The increased evidence obtained from cultured cells or animal experiments reveal a putative place for H2 treatment and its radioprotective effect clinically. This review focuses on major scientific advances of in the treatment of H2 as a new class of radioprotective agents.

scholarly journals Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

2018 ◽  
Vol 45 (5) ◽  
pp. 1797-1806 ◽  
Author(s):  
Anbang Han ◽  
Yingdong Lu ◽  
Qi Zheng ◽  
Jian Zhang ◽  
YiZhou Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Signaling Pathways ◽  
Rat Model ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Protective Effects ◽  
Tnf Α ◽  
Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

The impact of pre-radiotherapy surgical intervention on radiation-induced lung injury

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 7274-7274
Author(s):  
L. B. Marks ◽  
Z. Kocak ◽  
X. Yu ◽  
S. Zhou ◽  
D. Hollis ◽  
...  
Keyword(s):  
Lung Injury ◽  
Surgical Intervention ◽  
Radiation Induced ◽  
The Impact

scholarly journals TGF-β1 protects intestinal integrity and influences Smads and MAPK signal pathways in IPEC-J2 after TNF-α challenge

2017 ◽  
Vol 23 (3) ◽  
pp. 276-284 ◽  
Author(s):  
Kan Xiao ◽  
Shuting Cao ◽  
Lefei Jiao ◽  
Zehe Song ◽  
Jianjun Lu ◽  
...  
Keyword(s):  
Epithelial Barrier ◽  
Control Group ◽  
Signal Pathways ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Protein Activation ◽  
Intestinal Integrity ◽  
Tnf Α ◽  
Tgf Β1

The aim of this study was to investigate the protective effects of TGF-β1 on intestinal epithelial barrier, as well as canonical Smad and MAPK signal pathways involved in these protection processes by a IPEC-J2 model stimulated with TNF-α. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of TGF-β1. The results showed that TGF-β1 pretreatment ameliorated TNF-α-induced intestinal epithelial barrier disturbances as indicated by decrease of transepithelial electrical resistance (TER) and increase of paracellular permeability. TGF-β1 also dramatically alleviated TNF-α-induced alteration of TJ proteins ZO-1 and occludin. Moreover, TGF-β1 pretreatment increased TβRII protein expression in IPEC-J2 monolayers challenged with TNF-α. In addition, a significant increase of Smad4 and Smad7 mRNA was also observed in the TGF-β1 pretreatment after TNF-α challenge compared with the control group. Furthermore, TGF-β1 pretreatment enhanced smad2 protein activation. These results indicated that the canonical Smad signaling pathway was activated by TGF-β1 pretreatment. Finally, TGF-β1 pretreatment decreased the ratios of the phosphorylated to total JNK and p38 (p-JNK/JNK and p-p38/p38) and increased the ratio of ERK (p-ERK/ERK). Anti-TGF-β1 Abs reduced these TGF-β1 effects. These results indicated that TGF-β1 protects intestinal integrity and influences Smad and MAPK signal pathways in IPEC-J2 after TNF-α challenge.

scholarly journals Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
An-qi Ren ◽  
Hui-jun Wang ◽  
Hai-yan Zhu ◽  
Guan Ye ◽  
Kun Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blot ◽  
Mononuclear Cells ◽  
Macrophage Polarization ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Tnf Α

Background and Aims:Rabdosia japonica var. glaucocalyx is a traditional Chinese medicine (TCM) for various inflammatory diseases. This present work aimed to investigate the protective effects of R. japonica var. glaucocalyx glycoproteins on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism.Methods: Glycoproteins (XPS) were isolated from R. japonica var. glaucocalyx, and homogeneous glycoprotein (XPS5-1) was purified from XPS. ANA-1 cells were used to observe the effect of glycoproteins on the secretion of inflammatory mediators by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assay, immunofluorescence assay, and Western blot analysis were performed to detect macrophage polarization in vitro. The ALI model was induced by LPS via intratracheal instillation, and XPS (20, 40, and 80 mg/kg) was administered intragastrically 2 h later. The mechanisms of XPS against ALI were investigated by Western blot, ELISA, and immunohistochemistry.Results:In vitro, XPS and XPS5-1 downregulated LPS-induced proinflammatory mediators production including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and nitric oxide (NO) and upregulated LPS-induced IL-10 secretion. The LPS-stimulated macrophage polarization was also modulated from M1 to M2. In vivo, XPS maintained pulmonary histology with significantly reducing protein concentration and numbers of mononuclear cells in bronchoalveolar lavage fluid (BALF). The level of IL-10 in BALF was upregulated by XPS treatment. The level of cytokines including TNF-α, IL-1β, and IL-6 was downregulated. XPS also decreased infiltration of macrophages and polymorphonuclear leukocytes (PMNs) in lung. XPS suppressed the expression of key proteins in the TLR4/NF-κB signal pathway.Conclusion: XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of R. japonica var. glaucocalyx in inflammation-linked diseases.

scholarly journals Mouse Mesenchymal Stem Cell-derived Exosomal Mir-466f-3p Reverses Emt Process Through Inhibiting Akt/gsk3β Pathway via C-met in Radiation-induced Lung Injury

2022 ◽  
Author(s):  
Yi Li ◽  
Zhufu Shen ◽  
Xiao Jiang ◽  
Yuanyuan Wang ◽  
Zuozhang Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lung Injury ◽  
Lung Fibrosis ◽  
Luciferase Assay ◽  
Mechanistic Study ◽  
Protective Effects ◽  
Mesenchymal Transition ◽  
Radiation Induced

Abstract Background: Radiation-induced lung fibrosis (RILF) is a common complication of thoracic radiotherapy. Alveolar epithelial cells play a crucial role in lung fibrosis via epithelial-mesenchymal transition (EMT). Exosomes derived from mesenchymal stem cells own the beneficial properties to repair and regeneration of damaged tissues, however the underlying mechanisms remain poorly understood. Methods: Mouse mesenchymal stem cells-derived exosomes (mMSCs-Exo) were isolated by differential centrifugation, and their protective effects were assessed in vivo and in vitro , respectively. EMT-associated proteins were measured via western blot assay and/or immunofluorescence staining. The miRNA expression was measured by microarray assay and qPCR. Furthermore, bioinformatics prediction with KEGG analysis, luciferase assay, and rescue experiments were performed to explore the molecular mechanism underlying miR-466f-3p. Results: mMSCs-Exos were efficiently isolated ranging from 90-150 nm with high expression of exosomal markers (CD63, TSG101, and CD9). mMSCs-Exos administration efficiently relieved radiation-induced lung injury with less collagen deposition and lower levels of IL-1β and IL-6. Meanwhile, in vitro results showed mMSCs-Exos treatment obviously reversed EMT process induced by radiation. Among enriched miRNA cargo in exosomes, miR-466f-3p was primarily responsible for the protective effects via inhibition of AKT/GSK3β pathway. Our mechanistic study further demonstrated that c-MET was the direct target of miR-466f-3p, whose restoration partially abrogated mMSCs-Exo-mediated inhibition in both EMT process and AKT/GSK3β signaling activity induced by radiation. Conclusions: Our findings indicated that exosomal miR-466f-3p derived from mMSCs may possess anti-fibrotic properties and prevent radiation-induced EMT through inhibition of AKT/GSK3β via c-MET, providing a promising therapeutic modality for radiation-induced lung fibrosis.

scholarly journals Oxidative Stress and Inflammation Induced by Waterpipe Tobacco Smoking Despite Possible Protective Effects of Exercise Training: A Review of the Literature

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 777 ◽  
Author(s):  
Behzad Taati ◽  
Hamid Arazi ◽  
Katsuhiko Suzuki
Keyword(s):  
Oxidative Stress ◽  
Exercise Training ◽  
Tobacco Smoking ◽  
Relaxation Method ◽  
The Body ◽  
Protective Effects ◽  
Respiratory Problems ◽  
Risk Of Mortality ◽  
Waterpipe Tobacco Smoking ◽  
The Impact

The prevalence of waterpipe tobacco smoking (WTS), which is also known as ghalyan, shisha or hookah, is increasing rapidly around the world, especially among youth. Growing interest in this form of tobacco smoking can be traced, in part, to the use of flavored tobacco products, social acceptability as a safer option than cigarettes, and its consideration as a relaxation method or entertainment. However, there is a well-established association between WTS and oxidative stress that causes irreversible chronic pathological conditions such as cardiovascular and respiratory problems, as well as different types of cancers, and thus increases the risk of mortality. Clearly, induction of inflammation status through increased reactive oxygen species (ROS), which in turn leads to oxidative stress and harm to lipids, DNA, and proteins, is the most plausible mechanism to explain the potential harmful effects of WTS. Unlike WTS, well-designed exercise training programs increase ROS to the extent that it is beneficial to the body. In this study, we aimed to review available evidence on the impact of exercise training on oxidative stress and inflammation status. We also summarize the effect of acute and chronic WTS on different exercise capacities.

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