Pharmacological Modulation of Radiation Damage. Does It Exist a Chance for Other Substances than Hematopoietic Growth Factors and Cytokines?

Höfer, Milan; Hoferová, Zuzana; Falk, Martin

doi:10.3390/ijms18071385

Cited by 31 publications

(11 citation statements)

References 155 publications

(164 reference statements)

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“…In this technical sense, ideal radiomitigators ought to be anti-inflammatory, enhance antioxidant defenses, have antimutagenic properties, upregulate the DNA repair mechanisms, activate mitotic processes, cell growth and differentiation to promote the regeneration of damaged tissues, and forestall or reduce ARS and CRS. At present, no molecule under study meets all these prerequisites, but there are a large number of choices [ 54 , 233 , 234 ], which may be combined, for quick administration to affected individuals. For such situations, we may recommend the following:…”

Section: Medical Countermeasuresmentioning

confidence: 99%

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

et al. 2022

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Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms.

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Section: Medical Countermeasuresmentioning

confidence: 99%

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

et al. 2022

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“…Several promising strategies are continuously being developed to improve radiotherapy. For instance, spatial dose fractionation, time dose fractionation, micro/mini-beam irradiation, heavy-ion irradiation [10,11,12,13,14,15,16,17], and application of normal cell radio-protectants [18,19] and/or tumor cell radiosensitizers [20] could already be used in practice and eventually combined. One of the radiosensitizing approaches proposed is to selectively potentiate radiation toxicity for tumor cells by metal nanoparticles [21,22,23,24,25,26,27,28].…”

Section: Introductionmentioning

confidence: 99%

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Pagáčová

Štefančíková

Schmidt-Kaler

et al. 2019

IJMS

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From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the “physics” behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)), cancer cell types (HeLa, U87, and SKBr3), and doses (up to 4 Gy) of low-Linear Energy Transfer (LET) ionizing radiation (γ- and X-rays) on the extent, complexity and reparability of radiation-induced γH2AX + 53BP1 foci, the markers of double stand breaks (DSBs). Firstly, we sensitively compared the focus presence in nuclei during a long period of time post-irradiation (24 h) in spatially (three-dimensionally, 3D) fixed cells incubated and non-incubated with Pt nanoparticles by means of high-resolution immunofluorescence confocal microscopy. The data were compared with our preliminary results obtained for Au nanoparticles and recently published results for gadolinium (Gd) nanoparticles of approximately the same size (2–3 nm). Next, we introduced a novel super-resolution approach—single molecule localization microscopy (SMLM)—to study the internal structure of the repair foci. In these experiments, 10 nm Au nanoparticles were used that could be also visualized by SMLM. Altogether, the data show that different nanoparticles may or may not enhance radiation damage to DNA, so multi-parameter effects have to be considered to better interpret the radiosensitization. Based on these findings, we discussed on conclusions and contradictions related to the effectiveness and presumptive mechanisms of the cell radiosensitization by nanoparticles. We also demonstrate that SMLM offers new perspectives to study internal structures of repair foci with the goal to better evaluate potential differences in DNA damage patterns.

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“…Therefore, there is an urgent need to examine the ideal prevention strategies which function to protect the entire ovarian milieu from radiation damage [12]. Some nonpharmacologic [13, 14] and pharmacologic strategies [15] have been tried in an attempt to ameliorate the gonadotoxic effect of irradiation. However, the ideal mitigation paradigm has not been discovered yet.…”

Section: Introductionmentioning

confidence: 99%

Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

Mahran

Badr

Aldosari

et al. 2019

Oxidative Medicine and Cellular Longevity

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Premature ovarian failure (POF) is a common cause of infertility in premenopausal women who are unavoidably exposed to cytotoxic therapy. Radiotherapy is one of the most effective cytotoxic treatments. However, the radiosensitivity of ovarian tissues limits its therapeutic outcome and results in the depletion of the primordial follicle and loss of fertility. Therefore, the need for an effective radioprotective therapy is evident especially when none of the current clinically used modalities for radioprotection succeeds efficiently. The present study investigated the potential radioprotective effect of carvacrol (CAR) (80 mg) or thymol (80 mg) on gamma- (γ-) irradiation-induced ovarian damage as well as their role in the cross-talk between IGF-1 and TNF-α signaling and antioxidative activity. In immature female Wister rats, a single dose of whole-body irradiation (3.2 Gy, LD20) produced considerable ovarian damage, which was evident by histopathological findings and hormonal changes. Interestingly, pretreatment with CAR or thymol significantly enhanced the follicular development and restored the anti-Mullerian hormone (AMH), E2, and FSH levels. Both essential oils improved the irradiation-mediated oxidative stress and reduction in proliferating cell nuclear antigen (PCNA) expression. Moreover, irradiated rats exhibited an inverse relationship between IGF-1 and TNF-α levels two days post irradiation, which was further inverted by the pretreatment with CAR and thymol and ought to contribute in their radioprotective mechanisms. In conclusion, CAR and thymol showed a radioprotective effect and rescued the ovarian reserve mainly through counteracting oxidative stress and the dysregulated cross-talk between IGF-1 and TNF-α.

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Pharmacological Modulation of Radiation Damage. Does It Exist a Chance for Other Substances than Hematopoietic Growth Factors and Cytokines?

Cited by 31 publications

References 155 publications

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

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