Search Results (295)

Background. Acute radiation injury to the small-intestinal mucosa and the hematopoietic system is a key determinant of early mortality after high-dose total-body irradiation. ε-Aminocaproic acid (EACA), a lysine analogue with antifibrinolytic properties, has been proposed as a potential radioprotective agent, but its effects on intestinal and hematologic injury remain insufficiently characterized. Methods. In this experimental study, 240 male Wistar rats were subjected to single-dose total-body γ-irradiation at 10.6 Gy and randomized into six groups: two non-irradiated controls (CG-1, CG-2), an irradiated control without treatment (CG-3), and three experimental groups receiving EACA (EG-1: 3 h before irradiation; EG-2: 3 h after irradiation; EG-3: both 3 h before and 3 h after irradiation). Pain behavior was assessed using the Rat Grimace Scale. Intestinal damage was evaluated by a modified Radiation Injury Intestinal Mucosal Damage Score (RIIMS_sum), villus and crypt morphometry, and qualitative histology of the ileum. Hemoglobin, leukocytes, and platelets were measured serially, and 30-day survival was analyzed using Kaplan–Meier curves with log-rank tests. Results. Across all EACA regimens, the odds of being in a higher Rat Grimace Scale pain category were reduced compared with CG-3, with the strongest effect in EG-3 (OR 0.42; 95% CI 0.31–0.58). At 72 h after irradiation, the cumulative RIIMS score was lower in EACA-treated groups by approximately 17–36% versus CG-3, with the lowest injury in EG-3 (18.5 vs. 29.0 points). EACA attenuated shortening and blunting of villi, preserved crypt architecture, and mitigated anemia, leukopenia, and thrombocytopenia. Thirty-day survival was 20% in CG-3 and 60%, 65%, and 80% in EG-1, EG-2, and EG-3, respectively (all p < 0.05 vs. CG-3). Conclusions. ε-Aminocaproic acid exerts a pronounced, timing-dependent radioprotective effect in a rat model of acute total-body γ-irradiation, concurrently reducing the severity of radiation enteritis, hematologic toxicity, and early mortality. These findings support further investigation of EACA as a candidate adjunct in the prevention of acute radiation injury. Full article

Melanin pigments are ubiquitous biopolymers across diverse life forms and play multifaceted roles in cellular defense and environmental adaptation. The specialized neuromelanin in human brains accumulates mainly within catecholaminergic neurons of the substantia nigra and locus coeruleus, serving as a crucial modulator of brain homeostasis, metal detoxification, and oxidative stress responses. The intricate processes of human melanogenesis, encompassing both cutaneous and neuronal forms, are governed by complex genetic networks. Concurrently, melanin in fungi (synthesized through distinct genetic pathways) confers remarkable resistance to environmental stressors, including ionizing radiation. Recent advancements in omics technologies—including transcriptomics, proteomics, metabolomics, and epigenomics—have profoundly enhanced our understanding of neuromelanin’s molecular environment in health, aging, and neurodegenerative conditions such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and other neurological disorders. This article reviews the genetic underpinnings of human melanogenesis and fungal melanogenesis, explores the convergent and divergent evolutionary pressures driving their functions, and synthesizes the rapidly accumulating omics data to elucidate neuromelanin’s critical, and often dual, role in human brain pathology. Moreover, we discuss the intriguing parallels between neuromelanin and fungal melanin, highlighting radioprotection and its potential implications for neuroprotection and astrobiology, with a special emphasis on the need to investigate neuromelanin’s potential for radioprotection in light of fungal melanin’s remarkable protective properties. Full article

A high-purity alkaloid-enriched extract (NPAE) was developed from Nelumbinis Plumula. Beyond quantifying its representative alkaloids and total alkaloid content, this study revealed the novel radioprotective role of NPAE against radiation-induced oxidative stress in human umbilical vein endothelial cells (HUVECs). Pretreatment with NPAE significantly attenuated H₂O₂-induced oxidative stress and suppressed irradiation-induced pyroptosis, primarily through restoration of redox homeostasis and inhibition of inflammasome activation. Mechanistic investigations showed that NPAE downregulated the expression of GSDMD-N and cleaved caspase-1, while reducing the secretion of proinflammatory cytokines (IL-18 and IL-1β). These results demonstrate that NPAE effectively alleviates oxidative damage and prevents pyroptosis in endothelial cells, highlighting its potential as a promising phytotherapeutic agent for protection against ionizing radiation injury. Full article

Radiotherapy is a fundamental component in the management of head and neck malignancies, but its non-selective effects on surrounding normal tissues can result in significant oral complications. The oral cavity and oropharynx contain several radiosensitive structures, including mucosa, salivary glands, and alveolar bone, which are susceptible to both acute and late toxicities resulting in mucositis, xerostomia, and osteoradionecrosis. Although dentomaxillofacial diagnostic imaging, such as intraoral radiography, panoramic imaging and cone-beam computed tomography (CBCT), delivers radiation doses several orders of magnitude lower than therapeutic exposures, its biological impact on previously irradiated tissues remains underexplored. Even low-dose X-rays may act as secondary stressors, reactivating oxidative and inflammatory pathways in tissues with compromised repair capacity. In this review, we examine the radiobiological and dosimetric implications of using diagnostic ionizing imaging in patients undergoing or recently having completed head and neck radiotherapy. We summarize current evidence on potential additive effects of low-dose imaging, emphasizing the importance of justification, timing, and protocol optimization. Finally, we discuss radioprotective strategies (e.g., dose modulation, field limitation, and integration of modern low-dose imaging technologies) designed to reduce unnecessary exposure, thus enhancing tissue preservation and ensuring diagnostic safety in this vulnerable patient population Full article

Background: Agents with free radical-scavenging functions may act as radiation modifiers, protectors, or mitigators. Methods: We investigated whether supplementation with resveratrol (RSV) in mice, at different times after the beginning of X-irradiation, may influence sperm count and quality during the irradiation and recovery. Results: Irradiation importantly decreased the sperm count. RSV supplemented with 1 Gy since 24 h increased sperm count. The combination of low doses increased, whereas the combination of high doses reduced DNA damage. Coadministration of two high doses since the eighth day significantly increased DNA damage and slightly increased sperm count. The supplementation of RSV during recovery was toxic to irradiated males. The sperm parameters were a little better in the absence of RSV. The degree of DNA injury of germ cells was importantly lower in groups combined with 1 Gy. Conclusions: Resveratrol counteracted the radiation-induced death of germ cells and improved the sperm count. RSV may function as radioprotector (before or during exposure) and radiomitigator (after exposure) of lethal effects in male gametes. The combination of high doses of irradiation with RSV over 24 h mitigated DNA damage. Contrarily, supplementation during recovery is not recommended since it may be toxic during long-lasting irradiation. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcription factor that controls the antioxidant response to oxidative stress, especially after exposure to ionizing radiation (IR). This review examines NRF2’s emerging role as a complementary biomarker in radiobiological dosimetry for assessing radiation exposure and its potential health effects. When cells encounter IR, the resulting reactive oxygen species (ROS) interfere with the NRF2 repressor KEAP1, leading to NRF2 activation and the expression of cytoprotective genes such as HO-1, NQO1, and GCLC. Evidence suggests that NRF2 levels increase in a dose- and time-dependent manner, primarily at low to moderate radiation doses, highlighting its potential for early detection of radiation exposure. However, at high doses (>8 Gy), NRF2 activation may be suppressed due to apoptosis or irreversible damage, which limits its reliability in those situations. The review also compares NRF2 with other biomarkers used in biodosimetry, discussing its advantages, such as sensitivity and early response, along with its limitations, including variability in activation at high doses and expression influenced by other oxidative factors. The authors introduce a comprehensive radiobiological model that illustrates how low-dose IR exposure affects NRF2 expression patterns, thereby improving the understanding of dose-dependent oxidative stress mechanisms. Additionally, the role of NRF2 in inflammation and general health risk assessment is emphasized, suggesting broader applications beyond biodosimetry. Overall, NRF2 holds significant promise for use in evaluating radiation exposure, developing radioprotection strategies, and informing future radiobiological research frameworks. Full article

It is inevitable for life on earth to be exposed to various types of ionizing and non-ionizing radiation, underscoring the importance of radioprotection. The symbiotic interaction between gut microbiota and the host provides a strategy for protecting the organism against these stressors. However, the genetic mechanisms underlying this interaction remain poorly understood due to the complexity and diversity of gut microbiota. In this study, we employed a symbiotic experimental system involving Caenorhabditis elegans and Escherichia coli to systemically investigate the effects of bacterial genetic alterations on host responses to radiation exposure. Our findings revealed that deletion of the bacterial ybfQ gene (ΔybfQ) significantly enhanced worm tolerance to UV-B radiation. Transcriptomic analysis demonstrated an enhanced antioxidant capacity in ΔybfQ-fed worms, as evidenced by reduced levels of reactive oxygen species (ROS) and restored oxidative homeostasis. Notably, ΔybfQ bacteria exhibited overproduction of isoscoparin, and exogenous supplementation with isoscoparin similarly enhanced worm radio-tolerance, underscoring its crucial role in ΔybfQ-mediated antioxidant of host worm. Both interventions retained their protective effects in IIS-deficient worms (daf-16). However, the protective effects of ΔybfQ feeding, but not isoscoparin treatment, were attenuated in daf-2 worms with a constitutively activated IIS pathway, accompanied by reduced bacteria gut colonization. Collectively, our results provide novel insights into the genetic basis of host-microbe interactions and propose a potential pharmacological strategy for radiation protection. Full article

Background/Objectives: Kaempferol (KAE) is used to treat gamma radiation-induced damage. However, poor water solubility of KAE restricts its application. Therefore, we developed a KAE-loaded zeolitic imidazolate framework-8 (KAE@ZIF-8) to improve the solubility and bioavailability of KAE, thereby enhancing the radioprotective effect against gamma radiation. Methods: The composite was characterized using scanning electron microscopy (SEM), nitrogen adsorption/desorption analysis, X-ray diffraction (XRD), differential scanning calorimetry (DSC), equilibrium solubility assessments, in vitro release studies, stability evaluations, and drug-loading capacity measurements. The cytotoxic effects of KAE@ZIF-8 on Caco-2 cells were assessed in vitro. Meanwhile, the bioavailability of the preparation was also investigated. Finally, the protective efficacy of KAE@ZIF-8 against total body irradiation was evaluated in C57BL/6 mice. Results: The results indicated that KAE@ZIF-8 was successfully constructed, exhibiting a uniform hexagonal crystal morphology, with KAE transitioning from a crystalline to an amorphous state. As a carrier, ZIF-8 significantly enhanced the solubility of KAE by 9.2-fold, and the cumulative release within 12 h reached approximately 89%. Meanwhile, ZIF-8 could significantly enhance the bioavailability of KAE and reduce its toxicity. We found that pretreatment with KAE@ZIF-8 prolonged mouse survival time after 9 Gy total body irradiation (TBI). Mice were scarified on the 7th day after 7 Gy TBI. Results showed that KAE@ZIF-8 exhibited an improvement of the radioprotective effects, including weight loss mitigation, spleen index increase, radiation-induced intestinal injury attenuation, and modulation expression of IL-1β, IL-6, TNF-α and TGF-β1 following radiation. Conclusions: These results suggest the potential effect of ZIF-8 as an oral drug delivery carrier for radioprotective drugs. Full article

Radioprotective agents derived from natural food sources represent promising candidates for reducing the harmful effects of ionizing radiation and supporting healthy aging. In this study, we investigated the effects of selected micronized bioactive compounds and their mixes on DNA damage response pathways in human retinal epithelial cells (hTERT-RPE1). Individual compounds and their combinations were applied to cultured cells, and the expression of IER5, a radiation-inducible gene associated with DNA repair and cell survival, was evaluated, showing that most potent compound to be lycopene and quercetin. Thus, in the next step, commonly consumed foods available on the Czech market rich in moth—tomato and garlic—were analyzed for their antioxidant capacity. The results revealed marked variability in antioxidant potential among food sources, with specific cultivars exhibiting significantly higher values. Importantly, experimental mixtures of pure and micronized compounds demonstrated distinct and sometimes opposing effects on IER5 expression. These findings indicate that the radioprotective activity of dietary antioxidants depends not only on the properties of individual compounds but also on their specific combinations. Our study provides evidence that phytochemicals such as quercetin, lycopene, but also partially resveratrol and curcumin can modulate DNA-repair-associated pathways and underscores their potential as combinatory agents in strategies aimed at promoting genomic stability and potentially healthy aging. Full article

Background: Subclinical hyperthyroidism grade 1 (SCH G1, TSH > 0.1 mU/L) is common in patients with thyroid unifocal autonomy (UFA) and associated with cardiovascular risks and increased mortality. While ¹³¹I radioiodine therapy (¹³¹I-RIT) effectively treats UFA, it frequently induces hypothyroidism, partly due to extra-nodular absorbed dose (AD) enhanced by residual TSH stimulation. Objective: We hypothesized that short-term LT3-induced TSH suppression at the time of RIT would promote long-term euthyroidism. Patients and Methods: A retrospective study was conducted on 95 UFA patients with SCH G1 (2001–2024). Patients underwent baseline and post-LT3 thyroid scintigraphy, and then received ¹³¹I-RIT with individualized dosimetry. Long-term bioclinical follow-up was achieved. Results: Short-term low-dose LT3 suppression caused no adverse events and significantly reduced TSH (0.45 to 0.047 mU/L). Whole-gland ¹²³I uptake decreased moderately (11.0 to 8.4%), while extra-nodular lobe uptake dropped markedly (1.77 to 0.73%) (all p < 0.0001). This focused activity on the UFA (2.5-fold increase), maintaining mean UFA AD (about 260 Gy) but reducing extra-nodular AD (61 to 37 Gy, p < 0.0001). Despite low ¹³¹I doses (mean 181 MBq), a dose–response relationship was observed: higher AD correlated with greater nodular lobe volume reduction (p < 0.033). At the 88-month follow-up, 93% of patients achieved normal thyroid function; one had persistent SCH G1, two were borderline hypothyroid, and two required LT4. Conclusions: ¹³¹I-RIT under brief LT3-induced TSH suppression induces sustained euthyroidism in SCH G1 with UFA. This simple, low-risk strategy reduces radioprotection concerns and is under evaluation to determine cardiovascular benefits. Full article

Galactic cosmic ray (GCR) radiation is a major barrier to human space exploration beyond Earth’s magnetic field protection. Mesenchymal stem cells (MSCs) are found in all organs and play a critical role in repair and regeneration of tissue. We engineered bone marrow-derived MSCs and evaluated their response to ionizing radiation exposure. Epidermal growth factor receptor (EGFR) expression by certain types of cancers has been shown to induce radioresistance. In this study, we tested the feasibility of transfecting MSCs to overexpress EGFR (eMSC-EGFR) and their capacity to tolerate and recover from X-ray exposure. Quantitative real-time PCR (qRT-PCR) and immunoblotting results confirmed the efficient transfection of EGFR into MSCs and EGFR protein production. eMSC-EGFR maintained characteristics of human MSCs as outlined by the International Society for Cell & Gene Therapy. Then, engineered MSCs were exposed to various dose rates of X-ray (1–20 Gy) to assess the potential radioprotective role of EGFR overexpression in MSCs. Post-irradiation analysis included evaluation of morphology, cell proliferation, viability, tumorigenic potential, and DNA damage. eMSC-EGFR showed signs of radioresistance compared to naïve MSCs when assessing relative proliferation one week following exposure to 1–8 Gy X-rays, and significantly lower DNA damage content 24 h after exposure to 4 Gy. We establish for the first time the efficient generation of EGFR overexpressing MSCs as a model for enhancing the human body to tolerate and recover from moderate dose radiation injury in long-term manned space travel. Full article

Resveratrol may protect against radiation by modulating cellular metabolism and enhancing the cellular response to stress. Here, we explored its effects on human cardiomyocytes exposed to ionizing radiation. Resveratrol (5 µM) was administered for 1, 7, and 30 days before a single 2 Gy dose of irradiation, and then radiation toxicity and changes in the proteome were evaluated. Extended resveratrol treatment (7 or 30 days) induced more profound proteomic changes than one-day treatment and partially counteracted toxic effects of radiation, leading to increased cell survival, reduced cell death, and fewer cells arrested in the G1 phase. Though resveratrol administration itself had a greater impact on the proteome than radiation alone, we identified three subsets of proteins differently affected by radiation depending on the resveratrol context. The first subset (84 differentially expressed proteins; DEPs) represented proteins influenced by radiation in all resveratrol pretreatment regimens. The second subset (228 DEPs), linked to DNA repair, cell cycle checkpoints, and apoptosis, was affected by radiation only in the absence of resveratrol preconditioning, indicating the compound’s protective effect. The third subset (252 DEPs) involved in metabolism regulation appeared only after extended resveratrol preconditioning. In conclusion, the results demonstrate that hypothetical time-dependent cardioprotective effects of resveratrol are linked to significant proteomic reprogramming of cardiomyocytes caused by long-term pretreatment. Full article

Carnosic acid (CA) is a phenolic diterpene with high antioxidant activity that supports its radioprotective capacity. This study aims to determine whether the radiosensitizing effect of CA established in B16F10 melanoma cells also occurs in other melanin-producing cells. Cell survival analysis, apoptosis, intracellular glutathione levels, and cell cycle progression were evaluated by comparing radiosensitive cells (PNT2) with radioresistant melanin-producing cells (MELAN A, SK-MEL-1, and B16F10). In PNT2 cells, CA exhibited radioprotective capacity, with 100% cell survival after exposure to 20 Gy of X-rays (p < 0.001), decreasing apoptosis (p < 0.001) and increasing the GSH/GSSG ratio (p < 0.01), without significant modification in cell cycle progression. However, CA administration to irradiated cells failed to exert radioprotection in MELAN A and SK-MEL-1 cells, and even doubled cell death in B16F10 cells (p < 0.001). Specifically, CA did not alter apoptosis or prevent the decrease in GSH/GSSG ratio in MELAN A and SK-MEL-1 cells, while it intensified radiation-induced cell cycle disruptions in all melanin-producing cells. All of these led to a loss of radioprotective capacity in the melanin-producing cells (MELAN A and SK-MEL-1) and even induced a radiosensitizing effect in B16F10 cells. Understanding the mechanisms of action of substances such as CA could promote new applications that protect healthy cells and exclusively damage neoplastic cells when both are present within the same irradiated volume in cancer patients requiring radiotherapy. Full article

Radiation is widely used in cancer therapy but also damages healthy tissues through oxidative stress or inflammation. In addition to cancer patients, many professionals are occupationally exposed to ionizing radiation (IR). Natural compounds, particularly polyphenols, have been increasingly investigated as potential radioprotective agents to minimize side effects in both patients and occupationally exposed individuals. This study evaluated the radioprotective effects of a polyphenol-rich extract blend derived from chokeberry, elderberry, blackcurrant, and evening primrose in female Balb/c mice exposed to acute IR. The animals were pre-treated with the blend (100 mg/kg) for 7 days prior to whole-body IR at 6 Gy. Hematological parameters, immune cell viability, TNF-α level, gene expression, lipid peroxidation, and tissue morphology were assessed by hematology analysis, flow cytometry, ELISA, qRT-PCR, MDA assay, and histology. IR significantly reduced leukocyte (3.22-fold; p < 0.0001) and platelet counts (1.37-fold; p < 0.0001), increased TNF-α levels (53.93%; p < 0.0001), and elevated oxidative stress. Pre-treatment with the blend restored hematological parameters, reduced pro-inflammatory cytokines, and normalized genes regulating oxidative stress and apoptosis. Histology confirmed preserved liver and kidney structures compared with irradiated controls. These findings highlight the polyphenol-rich extract blend as a promising natural radioprotective agent by modulating immune responses, reducing oxidative stress, and preserving tissue integrity. Full article

A growing interest is focused on the efficient production of deinoxanthin (DEIX) and its use as a bioactive antioxidant. Here, we produced DEIX from Deinococcus radiodurans and examined how DEIX regulates hydrogen peroxide (H₂O₂)-mediated oxidative behaviors in mouse-derived bone marrow (BM) stromal cells and BM monocytes. We also evaluated whether oral supplementation with DEIX has radioprotective potential against total body irradiation (TBI)-mediated impairments in growth, organs, survival, and hematopoietic development using a mouse model. The direct addition of DEIX recovered H₂O₂-mediated oxidative disorders in the proliferation and the balance between osteoblast and osteoclast activity of the BM-derived cells in a dose-dependent manner. We found that recovery was closely associated with the DEIX’s potencies to remove cellular reactive oxygen species and to restore the expression of key molecules that tightly control bone homeostasis. Long-term oral supplementation with DEIX (25 mg/kg body weight, once per day for 42 consecutive days) protected mice against sub-lethal TBI (5 Gy)-mediated decreases in organ and body weights and lifespan. Supplemental DEIX also inhibited TBI-mediated structural damage in organs and restored endogenous antioxidant defense systems in the liver of TBI-exposed mice. Moreover, supplemental DEIX recovered a dysregulated hematopoietic process in TBI-exposed mice. Collectively, our results introduce an efficient method to produce DEIX and demonstrate its potency to recover oxidative cellular complication in H₂O₂-exposed BM-derived cells. Overall, our findings suggest that DEIX is a great antioxidative molecule to prevent or protect TBI-mediated systemic damages. Full article