Radioprotectors – the Evergreen Topic

Kuntić, Vesna; Stanković, Miroslava; Vujić, Zorica; Brborić, Jasmina; Uskoković‐Marković, Snežana

doi:10.1002/cbdv.201300054

Cited by 48 publications

(30 citation statements)

References 69 publications

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“…This has made the development of effective and safe radioprotectors an important issue. The discovery of compounds with fewer toxic effects isolated from natural sources has enabled the identification of new potential radioprotective agents [63,64]. A traditional Chinese herb, Dragon's blood, and its extracts were found to show antioxidative and anti-inflammatory activities and effectively alleviate radiation-induced damage in bone marrow [65].…”

Section: Discussionmentioning

confidence: 99%

Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

Wang

Ahn

Alharbi

et al. 2020

IJMS

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The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20 Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1β, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury.

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Section: Discussionmentioning

confidence: 99%

Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

Wang

Ahn

Alharbi

et al. 2020

IJMS

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“…Although numerous compounds were tested for this purpose [26,27], amifostine is the only radioprotector that has been officially approved by the FDA for human use [28]. Unfortunately, this drug has not been widely used due to a variety of reasons such as cost, limited efficacy, and significant side effects (including hypotension, serious cutaneous reactions, nausea, vomiting, and anaphylaxis) and the need for daily IV administration [28].…”

Section: Discussionmentioning

confidence: 99%

p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan

Ganapathy

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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Purpose The main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. p53 activation is a major pathway by which normal tissues respond to DNA damaging agents such as chemotherapy and radiotherapy, resulting in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that the use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from 5-FU and X-ray. We have also demonstrated that LDA-mediated protection requires functional p53 and thus is selective to normal tissues, as essentially every cancer cell has dysfunctional p53. Here, we tested the protective efficacy of LDA for bone marrow tissue against radioimmunotherapy through animal experiments. Method and Materials Mice were subject to LDA pretreatment for three days, followed by Y-90 ibritumomab tiuxetan treatment. Both dose-course (10, 25, 50, 100 and 200 μCi) and time-course (6h, 24h, 72h, 1wk and 2wk) experiments were performed. The response of bone marrow cells to LDA was examined by examining the expression of NFκB, Glut1 and Glut3. H&E, γ-H2AX, and TUNEL staining was employed to examine morphology, DNA damage response and apoptotic cell populations. Results Elevated levels of NFκB, Glut1 and Glut3 were observed in bone marrow cells after LDA treatment. Bone marrow damages induced by Y-90 ibritumomab tiuxetan were greatly reduced by LDA pretreatment. Consistent with this observation, significantly less DNA damage and fewer apoptotic cells were accumulated after Y-90 ibritumomab tiuxetan treatment in LDA-pretreated mice. Furthermore, in the mouse xenograft model implanted with human Karpas-422 lymphoma cells, LDA pretreatment did not have any detectable effect on either tumor growth or Y-90 ibritumomab tiuxetan (200 μCi)-induced tumor suppression. Conclusions LDA pretreatment protected bone marrow without compromising tumor control caused by Y-90 ibritumomab tiuxetan.

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“…Cells may be affected by ionizing radiation directly or indirectly (21 (19,22). When these ROS interact with biomolecules, secondary free radicals may be produced, leading to cytotoxic events (23,24).…”

Section: Side Effects Of Radiotherapy and Need For Radioprotectorsmentioning

confidence: 99%

Effects of traditional oriental medicines as anti-cytotoxic agents in radiotherapy

et al. 2017

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Abstract. The primary goal of radiotherapy in oncology is to enhance the efficacy of tumor cell death while decreasing damage to surrounding normal cells. Positive therapeutic outcomes may be accomplished by improved targeting, precisely targeting tumor cells or protecting normal cells against radiation-induced damage. The potential for antioxidants to decrease normal tissue damage induced by radiation has been investigated in animal models for a number of decades. In attempts for radioprotection, certain synthetic chemicals are suggested as antioxidants and normal tissue protectors against radiation-induced damage, but they have exhibited limitations in pharmacological application due to undesirable effects and high toxicities at clinical doses. The present review focuses on the radioprotective efficacy of traditional oriental medicines with the advantage of low toxicity at pharmacological doses and how such treatments may influence various harmful effects induced by radiation in vitro and in vivo. In addition, medicinal plants and their active constituents with biological activities that may be associated with alleviation of radiation-induced damage through antioxidant, anti-inflammatory, wound healing and immunostimulatory properties are discussed.

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Radioprotectors – the Evergreen Topic

Cited by 48 publications

References 69 publications

Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan

Effects of traditional oriental medicines as anti-cytotoxic agents in radiotherapy

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