Protective effect of propolis in protecting against radiation-induced oxidative stress in the liver as a distant organ.

Stresses caused by ionizing radiation can also damage tissues and organs through the circulatory system. In this study, we aimed to determine the radioprotective effect of propolis, a natural and powerful antioxidant product, against oxidative liver damage caused by cranial irradiation. Thirty-two male albino Sprague-Dawley rats, divided into four groups, were designed as sham group, irradiation (IR) group, propolis plus IR, control group of propolis. Biochemical parameters were measured in liver tissue of rats. While Total enzymatic superoxide scavenging activity (TSSA) and non-enzymatic superoxide scavenging activity (NSSA), glutathione peroxidase (GSH-Px) activities of all groups were statistically significantly higher than rats receiving only-irradiation, Glutathione-S-transferase (GST) activity in the IR group was significantly lower than in the sham control group and IR + propolis group. Superoxide dismutase (SOD) activity in the IR group was found to be significantly higher than both the sham control group and the propolis control group, but lower than the IR + propolis group. Malondialdehyde level and xanthine oxidase activity were higher in the IR group than in the other groups. Compared to the sham control group, in the group treated with propolis, a significant elevation in antioxidant parameters, specifically TSSA, NSSA, SOD, and GST activities, was noted, with corresponding increases of 32.3%, 23.2%, 47.6%, and 22.6%, respectively. Our findings show that propolis can be a radioprotective agent against ionized radiation damage by increasing antioxidant activity and reducing oxidant stress in liver tissue.

N-formylmethionine-leucyl-phenylalanine protects against irradiation-induced damage to hematopoiesis and intestines.

BACKGROUND: Ionizing radiation (IR), including radiotherapy, can exert lasting harm on living organisms. While liposaccharide (LPS) offers resistance to radiation damage, it also induces toxic responses. Thankfully, an LPS analogue called N-formylmethionine-leucyl-phenylalanine (fMLP) holds the potential to mitigate this toxicity, offering hope for radiation protection. METHODS: Survival of C57BL/6 mice exposed to IR after administration with fMLP/LPS/WR-2721 or saline was recorded. Cell viability and apoptosis assay of bone marrow (BMC), spleen and small intestinal epithelial (HIECs) cells were tested by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Tissue damage was evaluated by Hematoxilin and Eosin (H&E), Ki-67, and TUNEL staining. RNA sequencing was performed to reveal potential mechanisms of fMLP-mediated radiation protection. Flow cytometry and western blot were performed to verify the radiation protection mechanism of fMLP on the cell cycle. RESULTS: The survival rates of C57BL/6 mice exposed to ionizing radiation after administering fMLP increased. fMLP demonstrated low toxicity in vitro and in vivo, maintaining cell viability and mitigating radiation-induced apoptosis. Moreover, it protected against tissue damage in the hematopoietic and intestinal system. RNA sequencing shed light on fMLP's potential mechanism, suggesting its role in modulating innate immunity and cell cycling. This was evidenced by its ability to reverse radiation-induced G2/M phase arrests in HIECs. CONCLUSION: fMLP serves as a promising radioprotective agent, preserving cells and radiosensitive tissues from IR. Through its influence on the cell cycle, particularly reversing radiation-induced arrest in G2/M phases, fMLP offers protection against IR's detrimental effects.

Enhancing radioprotection: exploring the impact of L-carnitine supplementation on the oxidative stress in the liver.

BACKGROUND: The adverse effects of radiotherapy (RT) primarily occur through oxidative stress, and attempts are being made to mitigate these effects. L-Carnitine (L-Car) involved in physiological functions, possesses antioxidant and tissue-protective properties. The goal of this investigation is to appraise the radioprotective efficacy of L-Car supplementation. METHODS AND RESULTS: The groups were established by dividing thirty-two rats as: control, RT (10 Gy), RT + L-Car (200 mg/kg/d), L-Car. Upon completion of the experiment, the livers were harvested for histopathological, immunostaining [tumor necrosis factor-alpha (TNF-α), Caspase-3], spectrophotometric [total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI)], and mRNA expression [(Nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap-1), Heme Oxygenase (HO-1), Transforming growth factor beta 1 (TGF-ß1)] analyses. In the damage group, decreased Keap-1, Nrf2, HO-1, and TAS values, along with increased histopathological findings, alanine transferase, aspartate transferase, TNF-α, Caspase-3, TOS, OSI, TGF-ß1 levels were found. All findings were improved with L-Car treatment. CONCLUSIONS: Considering these findings, it can be inferred that L-Car exhibits tissue-protective effects against organ damage predominantly induced by RT-related oxidative stress. Additionally, it has prevented the development of inflammation, apoptosis, and fibrosis. Therefore, L-Car may be considered as a supplement to reduce complications associated with RT.

Impact of dietary ingredients on radioprotection and radiosensitization: a comprehensive review.

Radiation exposure poses significant health risks, particularly in radiotherapy and nuclear accidents. Certain dietary ingredients offer potential radioprotection and radiosensitization. In this review, we explore the impact of dietary ingredients, including vitamins, minerals, antioxidants, and other bioactive compounds, on radiation sensitivity and their potential for radioprotection. Radiosensitizers reoxygenate hypoxic tumor cells, increase the radiolysis of water molecules, and regulate various molecular mechanisms to induce cytotoxicity and inhibit DNA repair in irradiated tumor cells. Several dietary ingredients, such as vitamins C, E, selenium, and phytochemicals, show promise in protecting against radiation by reducing radiation-induced oxidative stress, inflammation, and DNA damage. Radioprotectors, such as ascorbic acid, curcumin, resveratrol, and genistein, activate and modulate various signaling pathways, including Keap1-Nrf2, NF-κB, PI3K/Akt/mammalian target of rapamycin (mTOR), STAT3, and mitogen-activated protein kinase (MAPK), in response to radiation-induced oxidative stress, regulating inflammatory cytokine expression, and promoting DNA damage repair and cell survival. Conversely, natural dietary radiosensitizers impede these pathways by enhancing DNA damage and inducing apoptosis in irradiated tumor cells. Understanding the molecular basis of these effects may aid in the development of effective strategies for radioprotection and radiosensitization in cancer treatment. Dietary interventions have the potential to enhance the efficacy of radiation therapy and minimize the side effects associated with radiation exposure.

Effect of Selenium and Selenoproteins on Radiation Resistance.

With the advancement of radiological medicine and nuclear industry technology, radiation is increasingly used to diagnose human health disorders. However, large-scale nuclear leakage has heightened concerns about the impact on human organs and tissues. Selenium is an essential trace element that functions in the body mainly in the form of selenoproteins. Selenium and selenoproteins can protect against radiation by stimulating antioxidant actions, DNA repair functions, and immune enhancement. While studies on reducing radiation through antioxidants have been conducted for many years, the underlying mechanisms of selenium and selenoproteins as significant antioxidants in radiation damage mitigation remain incompletely understood. Therefore, this paper aims to provide new insights into developing safe and effective radiation protection agents by summarizing the anti-radiation mechanism of selenium and selenoproteins.

Oxytocin: A Shield against Radiation-Induced Lung Injury in Rats.

BACKGROUND: Radiation-induced lung injury (RILI), a serious side effect of thoracic radiotherapy, can lead to acute radiation pneumonitis (RP) and chronic pulmonary fibrosis (PF). Despite various interventions, no effective protocol exists to prevent pneumonitis. Oxytocin (OT), known for its anti-inflammatory, antiapoptotic, and antioxidant properties, has not been explored for its potential in mitigating RILI. MATERIALS AND METHODS: This study involved 24 female Wistar albino rats, divided into three groups: control group, radiation (RAD) + saline, and RAD + OT. The RAD groups received 18 Gy of whole-thorax irradiation. The RAD + OT group was treated with OT (0.1 mg/kg/day) intraperitoneally for 16 weeks. Computerizing tomography (CT) imaging and histopathological, biochemical, and blood gas analyses were performed to assess lung tissue damage and inflammation. RESULTS: Histopathological examination showed significant reduction in alveolar wall thickening, inflammation, and vascular changes in the RAD + OT group compared to the RAD + saline group. Biochemical analysis revealed decreased levels of TGF-beta, VEGF, and PDGF, and increased BMP-7 and prostacyclin in the RAD + oxytocin group (p < 0.05). Morphometric analysis indicated significant reductions in fibrosis, edema, and immune cell infiltration. CT imaging demonstrated near-normal lung parenchyma density in the RAD + oxytocin group (p < 0.001). CONCLUSION: Oxytocin administration significantly mitigates radiation-induced pneumonitis in rats, implying that is has potential as a therapeutic agent for preventing and treating RILI.

Nanoengineered Injectable Hydrogel: An Advanced Radioprotective Barrier with Magnetic Hyperthermia Synergy.

Despite its effectiveness in eradicating cancer cells, current tumor radiotherapy often causes irreversible damage to the surrounding healthy tissues. To address this issue and enhance therapeutic outcomes, we developed a multifunctional injectable hydrogel that integrates electromagnetic shielding and magnetothermal effects. This innovation aims to improve the efficacy of brachytherapy while protecting adjacent normal tissues. Recognizing the limitations of existing hydrogel materials in terms of stretchability, durability, and single functionality, we engineered a composite hydrogel by self-assembling nickel nanoparticles on the surface of liquid metal particles and embedding them into an injectable hydrogel matrix. The resulting composite material demonstrates superior electromagnetic interference shielding performance (74.89 dB) and a rapid magnetothermal heating rate (10.9 °C/min), significantly enhancing its in vivo applicability. The experimental results confirm that this innovative nanocomposite hydrogel effectively attenuates electromagnetic waves during brachytherapy, thereby protecting normal tissues surrounding the tumor and enhancing radiotherapy efficacy through magnetothermal therapy. This study advances the safety and effectiveness of cancer treatments and provides new insights into the development of multifunctional biomedical materials, promoting the innovative application of nanotechnology in the medical field.

Development and performance evaluation of medical radiation-reducing creams using eco-friendly radiation-shielding composites.

To ensure the safety of medical personnel in healthcare organizations, radiation-shielding materials like protective clothing are used to protect against low-dose radiation, such as scattered rays. The extremities, particularly the hands, are the most exposed to radiation. New materials that can be directly coated onto the skin would be more cost-effective, efficient, and convenient than gloves. We developed protective creams using eco-friendly shielding materials, including barium sulfate, bismuth oxide, and ytterbium oxide, to avoid harmful effects of heavy metals like lead, and tested their skin-protective effects. Particularly, the radiation-shielding effect of ytterbium oxide was compared with that of the other materials. As shielding material dispersion and layer thickness greatly affect the efficacy of radiation-shielding creams, we assessed dispersion in terms of the weight percentage (wt%). The effective radiation energy was reduced by 20% with a 1.0-mm increase in cream thickness. Ytterbium oxide had a higher radiation-shielding rate than the other two materials. A 28% difference in protective effect was observed with varying wt%, and the 45 wt% cream at 63.4 keV radiation achieved a 61.3% reduction rate. Higher content led to a more stable incident energy-reducing effect. In conclusion, ytterbium oxide shows potential as a radiation-shielding material for creams.

Panax notoginseng Saponins Ameliorate Gamma Radiation-Mediated Damages in Human Peripheral Blood Monocytes and Swiss Albino Mice.

In this study, the protective effects of Panax notoginseng saponins (PNS) against gamma radiation-induced DNA damage and associated physiological alterations in Swiss albino mice were investigated. Exposure to gamma radiation led to a dose-dependent increase in cytokinesis-blocked micronuclei (CBMN) double-strand DNA breaks (DSBs), dicentric aberrations (DC), formation in peripheral blood mononuclear cells. However, pretreatment with PNS at concentrations of 1, 5, and 10 µg/mL significantly attenuated the frequencies of DC and CBMN in a concentration-dependent manner. PNS administration before radiation exposure also reduced radiation-induced DSBs in BL, indicating protection against reactive oxygen species generation and DNA damage. Notably, pretreatment with PNS at 10 µg/mL prevented the overexpression of γ-H2AX, proteins associated with DNA damage response, in irradiated mice. In addition, in vivo studies showed intraperitoneal administration of PNS (25 mg/kg body weight) for 1 h before radiation exposure mitigated lipid peroxidation levels and restored antioxidant status, countering oxidative damage induced by gamma radiation. Furthermore, PNS pretreatment reversed the decrease in hemoglobin (Hb) content, white blood cell count, and red blood cell count in irradiated mice, indicating preservation of hematological parameters. Overall, PNS demonstrated an anticlastogenic effect by modulating radiation-induced DSBs and preventing oxidative damage, thus highlighting its potential as a protective agent against radiation-induced DNA damage and associated physiological alterations. Clinically, PNS will be beneficial for cancer patients undergoing radiotherapy, but their pharmacological properties and toxicity profiles need to be studied.

Exploring the protective effect and mechanism of icariside II on the bladder in a rat model of radiation cystitis based on transcriptome sequencing.

PURPOSE: Radiation cystitis (RC) is a complex and common complication after radiotherapy for pelvic cancer. Icariside II (ICAII) is a flavonoid compound extracted from Epimedium, a traditional Chinese medicine, with various pharmacological activities. The aim of the present study was to investigate the cysto-protective effects of ICAII in RC rats and its possible mechanisms. MATERIALS AND METHODS: A rat model of induced radiation cystitis using pelvic X-ray irradiation was used, and bladder function was assessed by bladder volume and bladder leakage point pressure (LPP) after ICAII treatment. HE and Masson stains were used to assess the histopathological changes in the bladder. IL-6, TNF-α, IL-10, IL-4 and IL-1ß were measured by ELISA to assess the level of inflammation. The gene-level changes in ICAII-treated RC were observed by transcriptome sequencing, and then the potential targets of action and biological mechanisms were explored by PPI, GO and KEGG enrichment analysis of the differentially expressed genes. Finally, the predicted targets of action were experimentally validated using immunohistochemistry, RT-qPCR, molecular docking and CETSA. RESULTS: ICAII significantly increased bladder volume and the LPP, ameliorated pathological damage to bladder tissues, decreased the levels of IL-6, TNF-α, and IL-1ß, and increased the levels of IL-10 and IL-4 in radiation-injured rats. A total of 90 differentially expressed genes were obtained by transcriptome sequencing, and PPI analysis identified H3F3C, ISG15, SPP1, and LCN2 as possible potential targets of action. GO and KEGG analyses revealed that these differentially expressed genes were mainly enriched in the pathways metabolism of xenobiotics by cytochrome P450, arachidonic acid metabolism, Staphylococcus aureus infection and chemical carcinogenesis - reactive oxygen species. Experimental validation showed that ICAII could significantly increase the expression of H3F3C and ISG15 and inhibit the expression of SPP1 and LCN2. ICAII binds well to H3F3C, ISG15, SPP1 and LCN2, with the best binding ability to H3F3C. Furthermore, ICAII inhibited the protein degradation of H3F3C in bladder epithelial cells. CONCLUSIONS: ICAII may alleviate the bladder inflammatory response and inhibit the fibrosis process of bladder tissues through the regulation of H3F3C, ISG15, SPP1, and LCN2 targets and has a protective effect on the bladder of radioinjured rats. In particular, H3F3C may be one of the most promising therapeutic targets.

Comparative Evaluation of the Radioprotective Properties of Copper Chlorophyllin, Trolox, and Indralin in an Experiment on Mice.

The radioprotective properties of copper chlorophyllin (100 and 150 µg/g), the standard antioxidant trolox (100 and 200 µg/g), and the standard radioprotector indralin (100 and 150 µg/g) were compared in male ICR mice (CD-1) subjected to whole-body irradiation (X-ray radiation) in doses of 6, 6.5, and 6.75 Gy. Animal survival was analyzed using the Kaplan-Meier method, and the significance of differences was evaluated using the log-rank test method. Dose change factors determined using the Phinney probit analysis were 1.1, 1.0, and 1.8 for chlorophyllin, trolox, and indralin at a dose of 100 µg/g body weight, respectively. The insignificant radioprotective properties of chlorophyllin and their absence in trolox when administered prophylactically do not rule out their possible radioprotective properties like a radiomodulator that protects the body after irradiation.

BIO 300: A Prophylactic Radiation Countermeasure for Acute Radiation Syndrome.

INTRODUCTION: Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation. MATERIALS AND METHODS: Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder. RESULTS: In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g., neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls. CONCLUSIONS: BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems.

Preliminary Promising Findings for Manganese Chloride as a Novel Radiation Countermeasure Against Acute Radiation Syndrome.

INTRODUCTION: Military members and first responders may, at moment's notice, be asked to assist in incidents that may result in radiation exposure such as Operation Tomadachi in which the U.S. Navy provided significant relief for the Fukushima Daiichi Nuclear Reactor accident in Japan after an earthquake and tsunami in 2011. We are also currently facing potential threats from nuclear power plants in the Ukraine should a power disruption to a nuclear plant interfere with cooling or other safety measures. Exposure to high doses of radiation results in acute radiation syndrome (ARS) characterized by symptoms arising from hematopoietic, gastrointestinal, and neurovascular injuries. Although there are mitigators FDA approved to treat ARS, there are currently no FDA-approved prophylactic medical interventions to help protect persons who may need to respond to radiation emergencies. There is strong evidence that manganese (Mn) has radiation protective efficacy as a promising prophylactic countermeasure. MATERIALS AND METHODS: All animal procedures were approved by the Institutional Animal Care and Use Committee. Male and female B6D2F1J mice, 10 to 11 weeks old, were used for neurotoxicity studies and temporal effects of Mn. Four groups were evaluated: (1) vehicle injection, (2) dose of 4.5 mg/kg for 3 days, (3) dose of 13.5 mg/kg, and (4) sham. Irradiated mice were exposed to 9.5 Gy whole body Co60 γ-radiation. MRI was performed with a high dose of manganese chloride (MnCl2) (150 mg/kg) to assess the distribution of the MnCl2. RESULTS: The mice have promising survival curves (highest survival-13.5 mg/kg dose over 3 days of MnCl2 at 80% [87% female, 73% male] P = 0.0004). The complete blood count (CBC) results demonstrated a typical hematopoietic response in all of the irradiated groups, followed by mildly accelerated recovery by day 28 in the treated groups. No difference between groups was measured by Rota Rod, DigiGait, and Y-maze. Histologic evaluation of the bone marrow sections in the group given 13.5 mg/kg dose over 3 days had the best return to cellularity at 80%. MRI showed a systemic distribution of MnCl2. DISCUSSION: The preliminary data suggest that a dose of 13.5 mg/kg of MnCl2 given over 3 days prior to exposure of radiation may have a protective benefit while not exhibiting the neurobehavioral problems. A countermeasure that can prophylactically protect emergency personnel entering an area contaminated with high levels of radiation is needed, especially in light that nuclear accidents are a continued global threat. There is a need for a protective agent with easy long-term storage, easy to transport, easy to administer, and low cost. Histologic evaluation supports the promising effect of MnCl2 in protecting tissue, especially the bone marrow using the dose given over 3 days (4.5 mg/kg per day) of MnCl2. CONCLUSIONS: Initial experiments show that MnCl2 is a promising safe and effective prophylactic countermeasure against ARS. MRI data support the systemic distribution of MnCl2 which is needed in order to protect multiple tissues in the body. The pathology data in bone marrow and the brain support faster recovery from radiation exposure in the treated animals and decreased organ damage.

Anti-Ceramide ScFv Prophylaxis for First Responders to a Limited Nuclear Attack.

BACKGROUND/AIMS: After 9/11, multiple government agencies instituted programs aimed at developing medical radiation countermeasures (MRCs) for two syndromes lethal within weeks of a limited nuclear attack; the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS). While re-purposing drugs that enhance marrow repopulation treats H-ARS, no mitigator protects GI tract. METHODS: We recently reported anti-ceramide 6B5 single-chain variable fragment (scFv) pre-treatment abrogates ongoing small intestinal endothelial apoptosis to rescue Lgr5+ stem cells, preventing GI-ARS lethality in C57B/L6J mice. Here, with US Department of Defense support, we provide evidence that humanized anti-ceramide scFv (CX-01) is a promising prophylactic MRC for first responders, who risk exposure upon entering a radiation-contaminated site. RESULTS: CX-01, when delivered up to 90 min before irradiation, is highly-effective in preventing small intestinal endothelial apoptosis in mice and lethality in both sexes. Unexpectedly, females require an ~2-fold higher CX-01 dose than males for full protection. CX-01 is effective subcutaneously and intramuscularly, a property critical for battlefield use. Increasing the maximally-effective dose 5-fold does not extend duration of bioeffectiveness. CONCLUSION: While CX-01 prevents GI-ARS lethality, structural modification to extend half-life may be necessary to optimize first responder prophylaxis.

BIO 300 Attenuates Whole Blood Transcriptome Changes in Mice Exposed to Total-Body Radiation.

Development of radiation medical countermeasures under the U.S. Food and Drug Administration Animal Rule requires the capability to translate an effective animal-to-human drug dose. One method of human dose translation is using a biomarker and determining drug doses that modulate the biomarker to the desired level. BIO 300 Oral Powder (BIO 300) is a prophylactic radiation medical countermeasure that is currently being developed following the Animal Rule. The present study aimed to identify biomarkers that can be used for human dose conversion by conducting transcriptomics of whole blood collected from BIO 300-treated CD2F1 mice in the presence and absence of total-body irradiation (TBI). Unirradiated mice were treated with vehicle or 50, 100, or 200 mg/kg BIO 300, and irradiated mice were treated with 200 mg/kg or BIO 300 or vehicle prior to TBI. Whole-blood samples were collected after the last dose of the drug and after irradiation. RNA sequencing demonstrated 100 and 200 mg/kg of BIO 300 doses caused significantly more differential gene expression at 48 h after drug dose compared to 50 mg/kg of BIO 300 (7648, 7680, and 55 significantly differently expressed genes, respectively). Interestingly, following TBI, there were no significantly differentially expressed genes between vehicle- and BIO 300-treated mice. Despite the lack of significant changes in gene expression, the transcriptomic profiles in both groups indicated differential changes in signaling pathways. Pathway analysis of the transcriptome profile from vehicle-treated/TBI mice revealed that many inflammatory signaling pathways were activated in these animals. Signaling pathways enriched in BIO 300-treated/TBI mice were involved in cellular stress and immune response and were predicted to be inhibited. In all, four signaling pathways of interest were identified that were differentially enriched in irradiated animals treated with BIO 300: pathogen-induced cytokine storm signaling, S100 family signaling, pulmonary fibrosis idiopathic signaling, and wound-healing signaling. These pathways should be explored to identify potential biomarkers of BIO 300 that can be used for human dose translation.

Mitochondrial Targeted Cerium Oxide Nanoclusters for Radiation Protection and Promoting Hematopoiesis.

Purpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection. Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF). Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway. Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.

Assessment of the Acute Toxicity of Chlorophyllin and Trolox for the Possibility of Studying Their Radioprotective Properties.

The acute toxicity of chlorophyllin and trolox upon intraperitoneal injection of their solutions was studied in male ICR (CD-1) mice. The LD50 of chlorophyllin was found to be 633±37.2 µg/g body weight, which is lower than the LD50 of established radioprotectors. Trolox is technically non-toxic under the conditions of our study. The results obtained highlight the need for a detailed study of the radioprotective properties of trolox and chlorophyllin.

Natural Guardians: Natural Compounds as Radioprotectors in Cancer Therapy.

Cancer remains a significant global health challenge, with millions of deaths attributed to it annually. Radiotherapy, a cornerstone in cancer treatment, aims to destroy cancer cells while minimizing harm to healthy tissues. However, the harmful effects of irradiation on normal cells present a formidable obstacle. To mitigate these effects, researchers have explored using radioprotectors and mitigators, including natural compounds derived from secondary plant metabolites. This review outlines the diverse classes of natural compounds, elucidating their roles as protectants of healthy cells. Furthermore, the review highlights the potential of these compounds as radioprotective agents capable of enhancing the body's resilience to radiation therapy. By integrating natural radioprotectors into cancer treatment regimens, clinicians may improve therapeutic outcomes while minimizing the adverse effects on healthy tissues. Ongoing research in this area holds promise for developing complementary strategies to optimize radiotherapy efficacy and enhance patient quality of life.

Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate.

Recombinant α1-microglobulin (A1M) is proposed as a protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 h or 7 d. The differential protein expression was analyzed with tandem mass spectrometry. The dosimetric estimation was based on 177Lu activity in the kidney. PHLDA3 was the most prominent radiation-responsive protein in kidney tissue. In general, no statistically significant difference in the expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, a tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation-induced protein expression early after exposure, and late effects should be further studied.