Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Xu, Yong; Zhai, Da; Goto, Shinji; Jingu, Keiichi; Li, Tao‐Sheng

doi:10.1093/jrr/rrab112

Cited by 11 publications

(8 citation statements)

References 39 publications

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“…Radiation can directly lead to cell death and apoptosis. 4,17 Nicaraven also partially decreased the expression of 53BP1 and caspase 3 in irradiated lungs, especially by post-irradiation administration. The main manifestations of the late stage of RILI are fibroblast proliferation and collagen deposition.…”

Section: Discussionmentioning

confidence: 88%

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Optimization on the dose and time of nicaraven administration for mitigating the side effects of radiotherapy in a preclinical tumor-bearing mouse model

Abdelghany

Sekiya

et al. 2022

Ther Adv Respir Dis

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Objective: Radiation-induced lung injury (RILI) is one of the serious complications of radiotherapy. We have recently demonstrated that nicaraven can effectively mitigate RILI in healthy mice. Here, we further tried to optimize the dose and time of nicaraven administration for alleviating the side effects of radiotherapy in tumor-bearing mice. Methods and results: A subcutaneous tumor model was established in the back of the chest in C57BL/6N mice by injecting Lewis lung cancer cells. Therapeutic thoracic irradiations were done, and placebo or different doses of nicaraven (20, 50, 100 mg/kg) were administrated intraperitoneally pre-irradiation (at almost 5–10 min before irradiation) or post-irradiation (within 5 min after irradiation). Mice that received radiotherapy and nicaraven were sacrificed on the 30th day, but control mice were sacrificed on the 15th day. Serum and lung tissues were collected for evaluation. Nicaraven significantly decreased the level of CCL8, but did not clearly change the levels of 8-OHdG, TGF-β, IL-1β, and IL-6 in serum. Besides these, nicaraven effectively decreased the levels of TGF-β, IL-1β, and SOD2 in the lungs, especially by post-irradiation administration with the dose of 20 mg/kg. Although there was no significant difference, the expression of SOD1, 53BP1, and caspase 3 was detected lower in the lungs of mice received nicaraven post-irradiation than that of pre-irradiation. Conclusion: According to our data, the administration of nicaraven at a relatively low dose soon after radiotherapy will be recommended for attenuating the side effects of radiotherapy.

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Section: Discussionmentioning

confidence: 88%

“… 16 Moreover, we have recently demonstrated that nicaraven can also effectively protect against RILI by suppressing the inflammatory response. 17 To further develop for clinical application, we herein aim to optimize the dose and time of nicaraven administration for attenuating the side effects of radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Optimization on the dose and time of nicaraven administration for mitigating the side effects of radiotherapy in a preclinical tumor-bearing mouse model

Abdelghany

Sekiya

et al. 2022

Ther Adv Respir Dis

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“…It is well known that radiation activates NF-κB, which is considered to be the master switch of the inflammatory response and involved in the regulation of many inflammation-related genes [ 9 , 10 ]. Radiation-induced NF-κB activation is known to be involved in the damage to a lot of normal tissues [ 18–21 ], but damage to the cochleae caused by the NF-κB-mediated inflammatory response had not been reported. Consequently we designed this animal experiment to explore the regulatory effects of an NF-κB-mediated inflammatory response in radiation-induced damage to the cochlea, in the hope of providing an experimental foundation for cochlear protection during radiotherapy for head and neck cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress arising from exposure to ionizing radiation might also contribute to NF-κB activation [ 11 , 15 ]. Radiation-induced NF-κB activation involved in damage to normal tissues in radiation fields has been studied, and there are reports that NF-κB activation mediates radiation-induced damage to organs including the lung [ 18 ], intestines [ 19 , 20 ] and testis [ 21 ]. However there have been no reports of radiation-induced NF-κB activation in relation to damage to the cochlea.…”

Section: Introductionmentioning

confidence: 99%

Radiation-induced NF-κB activation is involved in cochlear damage in mice via promotion of a local inflammatory response

Tong

et al. 2022

Journal of Radiation Research

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The radiation-induced inflammatory response is involved in radiation damage to the cochlea and causes sensorineural hearing loss (SNHL). NF-κB, as the master switch of the inflammatory response, regulates the expression of many inflammation-related genes and thus the inflammatory response. Therefore, in this study we used a mouse model to determine whether radiation-induced NF-κB activation is involved in damage to the cochlea and to investigate the underlying mechanism. Eventually, we found that NF-κB was activated after radiation of the cochleae and the activation reached a maximum at 2–6 h after radiation. And morphological analysis showed severe damage to the cochleae after radiation, but this damage was significantly ameliorated by JSH-23 (an inhibitor of NF-κB) pretreatment. Along with these morphological changes, the expression levels of proinflammatory molecules (including proinflammatory cytokines IL-6, TNF-α, COX-2 and inflammation-related proteins VCAM-1, MIP-1β) in the cochlear tissues were significantly increased after radiation, but were significantly decreased by JSH-23 pretreatment compared to radiation alone. Therefore, these results indicated that radiation-induced NF-κB activation was involved in damage to the cochleae and resultant SNHL via its promotion of the inflammatory response mediated by overexpression of some proinflammatory molecules in cochlear tissues, and inhibition of radiation-induced NF-κB was conducive to preventing such damage.

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“…In addition, OVOL2 overexpression signi cantly compromise the GLUT1 translocation and aerobic glycolysis induced by NF-κB signaling in NSCLC cells [33]. Inhibition of NF-κB and TGF-beta/pSmad2 pathways could effectively relieve the injury and restrain the in ammation in the irradiated lung [34].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Responses in Bronchial Epithelial Cells Exposed to Vanadium

Abdel-Moneim

Yang

2022

Preprint

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Vanadium exposure has the negative effect on lung health in human, whereas the detailed mechanisms of vanadium exposure-induced pulmonary toxicity are limited. Hence, the present study aimed to investigate the hub genes and signaling pathways related to sodium metavanadate (SMV)-induced pulmonary toxicity. The transcript expression profile GSE36684 was downloaded from Gene Expression Omnibus. The profile contained eight human bronchial epithelial cell (HBEC) samples including five SMV-treated and three control HBECs samples. Totally 455 differentially expressed genes (DEGs) were screened, especially 201 and 254 genes were up- and down-regulated in the HBECs treated with SMV. Gene ontology analysis suggested that the DEGs were mainly involved in signal transduction, the response to drug, cell proliferation, adhesion and migration. Pathway analysis demonstrated the DEGs were primarily participated in NF-κB, Wnt, MAPK, and PI3K-Akt signaling pathways. Moreover, the hub genes, including ITGA5, ITGB3, ITGA2, LAMC2, MMP2, and ITGA4, might contribute to SMV-induced pulmonary toxicity. Our study improves the understanding of the molecular mechanisms by which SMV induced the pulmonary toxicity.

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Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Cited by 11 publications

References 39 publications

Optimization on the dose and time of nicaraven administration for mitigating the side effects of radiotherapy in a preclinical tumor-bearing mouse model

Optimization on the dose and time of nicaraven administration for mitigating the side effects of radiotherapy in a preclinical tumor-bearing mouse model

Radiation-induced NF-κB activation is involved in cochlear damage in mice via promotion of a local inflammatory response

Gene Expression Responses in Bronchial Epithelial Cells Exposed to Vanadium

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