Targets for protection and mitigation of radiation injury

Khodamoradi, Ehsan; Hoseini‐Ghahfarokhi, Mojtaba; Amini, Peyman; Motevaseli, Elahe; Shabeeb, Dheyauldeen; Musa, Ahmed Eleojo; Najafi, Masoud; Farhood, Bagher

doi:10.1007/s00018-020-03479-x

Cited by 51 publications

(24 citation statements)

References 315 publications

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Section: Introductionmentioning

confidence: 99%

“…When RIF is severe, significant cosmetic and functional consequences may result which can substantially impact quality of life, including loss of range of motion and muscle strength6 . The pathogenesis of RIF is multifactorial and remains incompletely understood; however, emerging evidence has suggested that targeting pathways of inflammation, cell death, and reactive oxygen species (ROS) generation may mitigate the effects of radiation8 .An important contributor to RIF is the acute rise of ROS and apoptotic proteins, which have been found to be pathologically elevated in irradiated tissue9,10 . Other key factors contributing to excessive soft tissue fibrosis include activation of fibroblasts and damage to microvascular endothelial cells[11][12][13] , which are both exacerbated by ROS activity[14][15][16][17][18][19] .…”

mentioning

confidence: 99%

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Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis

Shen

Borrelli

Adem

et al. 2020

Sci Rep

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Radiation therapy can result in pathological fibrosis of healthy soft tissue. The iron chelator deferoxamine (DFO) has been shown to improve skin vascularization when injected into radiated tissue prior to fat grafting. Here, we evaluated whether topical DFO administration using a transdermal drug delivery system prior to and immediately following irradiation (IR) can mitigate the chronic effects of radiation damage to the skin. CD-1 nude immunodeficient mice were split into four experimental groups: (1) IR alone (IR only), (2) DFO treatment for two weeks after recovery from IR (DFO post-IR), (3) DFO prophylaxis with treatment through and post-IR (DFO ppx), or (4) no irradiation or DFO (No IR). Immediately following IR, reactive oxygen species and apoptotic markers were significantly decreased and laser doppler analysis revealed significantly improved skin perfusion in mice receiving prophylactic DFO. Six weeks following IR, mice in the DFO post-IR and DFO ppx groups had improved skin perfusion and increased vascularization. DFO-treated groups also had evidence of reduced dermal thickness and collagen fiber network organization akin to non-irradiated skin. Thus, transdermal delivery of DFO improves tissue perfusion and mitigates chronic radiation-induced skin fibrosis, highlighting a potential role for DFO in the treatment of oncological patients.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis

Shen

Borrelli

Adem

et al. 2020

Sci Rep

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“…Over the last few decades, many natural and synthetic compounds have been investigated for their potential as radioprotectors, mitigators, or therapeutics. In recent few decades, awareness in natural compounds as a potential source of radioprotectors has raised up, due to their ability to provide health benefits, less toxicity and common anti-inflammatory and antioxidant properties (Mun et al, 2018;Khodamoradi et al, 2020). Radioprotective effects to lung tissue have been demonstrated for numerous naturally occurring substances.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Radiation-Induced Lung Injury by Hyaluronic Acid Nanoparticles

et al. 2020

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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.

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“…So serious studies were carried on to provide evidence that, using free radical scavengers immediately before radiation exposure is a necessity to alleviate DNA damage and prevent cell death. Further research has led to a large number of experimental studies defining suitable radioprotectors (1) .…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic and immunological efficacy of nicotiflorin and rutin combination on gamma irradiated rats

Mohammed

Ahmed²,

Montaser³

2022

Int J Radiat Res

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Background: Cytogenetic and immunological damages after ionizing radiation exposure are critical factors that lead to many different events and consequences cascade reactions starting from inflammation, ending with cell damage. These biological events if not well controlled will lead to deleterious effects and cancer. The present study aimed to evaluate the efficacy of the Nicotiflorin and Rutin (NR) combination against drastic effects resulted from γ-irradiation. Materials and Methods: Rats were divided into four groups. (Control) group, (NR) group: treated with 20mg/kg body weight orally daily one dose for two weeks, (Irrad) group: rats exposed to 6Gy as a single dose, and (NR+ Irrad) group which treated with NR combination before irradiation. Detection of DNA damage was done with the Micronucleus test (MN) and Comet assay. Immunological responses were detected by assessing inflammatory cytokines Interluekines-1β (IL-1β), tumor necrosis factor (TNFα), and homeostasis maintenance cytokines . Results: Irradiated group recorded a significant increase in micronuclei (MNi) incidences and significant DNA fragmentation. As well, immunological parameters displayed a significant increase in all measured interleukins except IL-10 which recorded a significant decline. The group injected with NR before irradiation showed significant improvement in all measured parameters. Conclusion: The efficacy of the NR combination may be attributed to its dual protective effects (cytogenetic and immunological enhancement) against damage caused by γ-irradiation.

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Targets for protection and mitigation of radiation injury

Cited by 51 publications

References 315 publications

Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis

Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis

Attenuation of Radiation-Induced Lung Injury by Hyaluronic Acid Nanoparticles

Cytogenetic and immunological efficacy of nicotiflorin and rutin combination on gamma irradiated rats

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