Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.628
Filtrar
1.
Int J Mol Sci ; 25(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39000587

RESUMO

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.


Assuntos
alfa-Globulinas , Octreotida , Proteômica , Animais , alfa-Globulinas/metabolismo , Camundongos , Octreotida/farmacologia , Octreotida/análogos & derivados , Proteômica/métodos , Proteínas Recombinantes/farmacologia , Rim/metabolismo , Rim/efeitos da radiação , Rim/efeitos dos fármacos , Masculino , Medula Óssea/efeitos da radiação , Medula Óssea/metabolismo , Medula Óssea/efeitos dos fármacos , Órgãos em Risco/efeitos da radiação , Proteoma/metabolismo , Protetores contra Radiação/farmacologia
2.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000045

RESUMO

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.


Assuntos
Produtos Biológicos , Neoplasias , Protetores contra Radiação , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Protetores contra Radiação/uso terapêutico , Protetores contra Radiação/farmacologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Animais
3.
Bull Exp Biol Med ; 177(1): 44-46, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38955851

RESUMO

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.


Assuntos
Clorofilídeos , Cromanos , Camundongos Endogâmicos ICR , Protetores contra Radiação , Animais , Masculino , Protetores contra Radiação/farmacologia , Clorofilídeos/farmacologia , Cromanos/farmacologia , Camundongos , Dose Letal Mediana , Antioxidantes/farmacologia , Injeções Intraperitoneais
4.
PLoS One ; 19(7): e0307598, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39042641

RESUMO

Metformin is a biguanide currently used in the treatment of diabetes mellitus type 2. Besides its anti-glycemic effects, metformin has been reported to induce different cellular pleiotropic effects, depending on concentration and time of treatment. Here we report one administration of metformin (0.5 mM) has radioprotective effects in vitro on BJ human fibroblasts, increasing DNA damage repair and increasing SOD1 expression in the nucleus. Importantly, metformin (200 mg/kg) pre-administration for only 3 days in wild type 129/sv mice, decreases the formation of micronuclei in bone marrow cells and DNA damage in colon and lung tissues compared to control irradiated mice at sub-lethal and lethal doses, increasing the overall survival fraction by 37% after 10Gy total body irradiation. We next pre-treated with metformin and then exposed 129/sv mice, to a galactic cosmic rays simulation (GCRsim), at the NASA Space Radiation Laboratory (NSRL). We found metformin pre-treatment decreases the presence of bone marrow micronuclei and DNA damage in colon and lung tissues and an increase of 8-oxoguanine DNA glycosylase-1 (OGG1) expression. Our data highlight a radioprotective effect of metformin through an indirect modulation of the gene expression involved in the cellular detoxification rather than its effects on mitochondria.


Assuntos
Dano ao DNA , Hipoglicemiantes , Metformina , Protetores contra Radiação , Metformina/farmacologia , Animais , Camundongos , Humanos , Protetores contra Radiação/farmacologia , Hipoglicemiantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/efeitos da radiação , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Fibroblastos/metabolismo , Superóxido Dismutase/metabolismo , Linhagem Celular , Testes para Micronúcleos , Pulmão/efeitos dos fármacos , Pulmão/efeitos da radiação , Pulmão/patologia , Pulmão/metabolismo , Masculino
5.
Biomed Pharmacother ; 177: 117029, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38991305

RESUMO

Amifostine (AMF) as the first-line radiation protection drug, usually suffered from low compliance and short half-life upon clinical applications. The development of oral drug delivery system (DDS) for AMF is a promising solution. However, the inherent shortages of AMF present significant challenges in the design of suitable oral DDS. Here in this study, we utilized the ability of calcium ions to bind with AMF and prepared AMF loaded calcium carbonate (CC) core, CC/AMF, using phase transferred coprecipitation method. We further modified the CC/AMF using phospholipids to prepare AMF loaded lipid-calcium carbonate (LCC) hybrid nanoparticles (LCC/AMF) via a thin-film dispersion method. LCC/AMF combines the oral advantages of lipid nanoparticles with the drug-loading capabilities of CC, which was shown as uniform nano-sized formulation with decent stability in aqueous solution. With favorable intestinal transport and absorption effects, it effectively enhances the in vivo radiation protection efficacy of AMF through oral administration. More importantly, we further investigated the cellular accumulation profile and intracellular transport mechanism of LCC/AMF using MDCK and Caco-2 cell lines as models. This research not only alters the current administration method of AMF to enhance its convenience and compliance, but also provides insights and guidance for the development of more suitable oral DDS for AMF in the future.


Assuntos
Amifostina , Carbonato de Cálcio , Nanopartículas , Protetores contra Radiação , Carbonato de Cálcio/química , Administração Oral , Animais , Humanos , Células CACO-2 , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/química , Protetores contra Radiação/farmacologia , Protetores contra Radiação/farmacocinética , Nanopartículas/química , Amifostina/administração & dosagem , Amifostina/farmacologia , Cães , Lipídeos/química , Células Madin Darby de Rim Canino , Sistemas de Liberação de Medicamentos/métodos , Proteção Radiológica/métodos , Portadores de Fármacos/química
6.
Food Funct ; 15(15): 8116-8127, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39011610

RESUMO

Research on plant and animal peptides has garnered significant attention, but there is a lack of studies on the functional properties of Tenebrio molitor peptides, particularly in relation to their potential mitigating effect on radiation damage and the underlying mechanisms. This study aims to explore the protective effects of Tenebrio molitor peptides against radiation-induced damage. Mice were divided into five groups: normal, radiation model, and low-, medium-, and high-dose Tenebrio molitor peptide (TMP) groups (0.15 g per kg BW, 0.30 g per kg BW, and 0.60 g per kg BW). Various parameters such as blood cell counts, bone marrow DNA content, immune organ indices, serum levels of D-lactic acid, diamine oxidase (DAO), endotoxin (LPS), and inflammatory factors were assessed at 3 and 15 days post gamma irradiation. Additionally, the intestinal tissue morphology was examined through H&E staining, RT-qPCR experiments were conducted to analyze the expression of inflammatory factors in the intestine, and immunohistochemistry was utilized to evaluate the expression of tight junction proteins ZO-1 and Occludin in the intestine. The findings revealed that high-dose TMP significantly enhanced the hematopoietic system function in mice post radiation exposure, leading to increased spleen index, thymus index, blood cell counts, and bone marrow DNA production (p < 0.05). Moreover, TMP improved the intestinal barrier integrity and reduced the intestinal permeability. Mechanistic insights suggested that these peptides may safeguard intestinal barrier function by downregulating the gene expression of inflammatory factors TNF-α, IL-1ß, and IL-6, while upregulating the expression of tight junction proteins ZO-1 and Occludin (p < 0.05). Overall, supplementation with TMP mitigates radiation-induced intestinal damage by enhancing the hematopoietic system and the intestinal barrier, offering valuable insights for further investigations into the mechanisms underlying the protective effects of these peptides against ionizing radiation.


Assuntos
Mucosa Intestinal , Peptídeos , Tenebrio , Animais , Camundongos , Peptídeos/farmacologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos da radiação , Mucosa Intestinal/efeitos dos fármacos , Masculino , Sistema Hematopoético/efeitos dos fármacos , Sistema Hematopoético/efeitos da radiação , Protetores contra Radiação/farmacologia , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-1/genética , Raios gama/efeitos adversos , Ocludina/metabolismo , Ocludina/genética , Intestinos/efeitos dos fármacos , Intestinos/efeitos da radiação
7.
Int J Nanomedicine ; 19: 6463-6483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946882

RESUMO

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.


Assuntos
Apoptose , Cério , Hematopoese , Mitocôndrias , Espécies Reativas de Oxigênio , Cério/química , Cério/farmacologia , Animais , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Hematopoese/efeitos dos fármacos , Hematopoese/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Protetores contra Radiação/química , Humanos , Proteção Radiológica/métodos , Linhagem Celular
8.
Int J Radiat Biol ; 100(8): 1213-1225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39038272

RESUMO

PURPOSE: Nuclear applications are being increasingly used in various fields, necessitating studies to protect from radiation hazards and their effects. In this study, five different chemical structures of pyrazolo [3,4-b] pyridine derivatives were synthesized. The gamma and neutron radiation protective abilities of these samples were determined and demonstrated their potential use as ingredients in radioprotective drugs. MATERIAL AND METHODS: Gamma radiation absorption parameters were calculated both theoretical and experimental. Important attenuation parameters for fast neutrons (4.5 MeV energy radiation) were figured out using the Monte Carlo simulation Geant4 code. Additionally, experimental dose rates were measured for each sample and compared to those of Paraffin and high-density polyethylene, an organic substance. Besides, Ames/Salmonella test system was aimed to detecting genotoxicity features of pyrazolo pyridine derivatives. RESULTS: All results demonstrated that each sample possesses both gamma and neutron radiation attenuation capabilities. It was determined that sample PPC4 (C20H14BrN5) exhibited the highest gamma radiation attenuation capacity among all samples, while sample PPC2 (C22H20N6) displayed an excellent neutron stopping capacity. The genotoxic properties of pyrazolo[3,4-b] pyridine derivatives were examined using the Ames/Salmonella test, and as a result, it was determined that these substances did not exhibit genotoxic effects at test doses up to 5 mM. CONCLUSION: All obtained results indicate that all PPC (pyrazolo[3,4-b] pyridine derivatives) samples do not possess a toxic effect, and they can be utilized as an active substance for the development of a drug or cream with protective properties against both gamma and neutron radiations.


Assuntos
Raios gama , Nêutrons , Pirazóis , Piridinas , Protetores contra Radiação , Piridinas/química , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/toxicidade , Protetores contra Radiação/farmacologia , Protetores contra Radiação/química , Testes de Mutagenicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/efeitos da radiação , Relação Dose-Resposta à Radiação , Método de Monte Carlo
9.
Front Public Health ; 12: 1394023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887249

RESUMO

To date, few FDA-approved medical countermeasures are available for addressing hematopoietic acute radiation syndrome (H-ARS). In this study, we present our latest research findings focusing on the evaluation of a novel radiation mitigator known as the mitigating amino acid mixture (MAAM). MAAM is composed of five amino acids as the recently reported amino acid-based oral rehydration solution for mitigating gastrointestinal (GI)-ARS. CD2F1 male and female mice were exposed to 60Co-γ total body irradiation (TBI) at 9.0 or 9.5 Gy. Following irradiation, mice were orally administered with MAAM or a saline vehicle control once daily for a duration of 14 days, commencing 24 h after TBI. Mouse survival and body weight change were monitored for 30 days after irradiation. Complete blood counts (CBCs), bone marrow (BM) stem and progenitor cell survival (clonogenicity), and a serum cytokine antibody array were analyzed using samples from day 30 surviving mice. Our data revealed that MAAM treatment significantly enhanced survival rates in irradiated male CD2F1 mice, and the survival rate increased from 25% in the vehicle control group to 60% in the MAAM-treated group (p < 0.05) after 9.0 Gy TBI. The number of BM colonies significantly increased from 41.8 ± 6.4 /104 cells (in the vehicle group) to 78.5 ± 17.0 /104 cells (in the MAAM group) following 9.0 Gy TBI. Furthermore, MAAM treatment led to a decrease in the levels of six cytokines/proteins [cluster of differentiation 40 (CD40), interleukin (IL)-17A, C-X-C motif chemokine 10 (CXCL10/CRG-2), cutaneous T cell-attracting chemokine (CTACK), macrophage inflammatory protein (MIP)-3ß, and IL-1ß] and an increase in the levels of five other cytokines/proteins [IL-3Rß, IL-5, leptin, IL-6, and stem cell factor (SCF)] in mouse serum compared to the vehicle group after 9.0 Gy TBI. However, similar alleviating effects of MAAM were not observed in the irradiated CD2F1 female mice. The serum cytokine profile in the irradiated female mice was different compared to the irradiated male mice. In summary, our data suggest that the beneficial effects of the mitigative amino acid combination treatment after radiation exposure may depend on sex.


Assuntos
Aminoácidos , Irradiação Corporal Total , Animais , Feminino , Masculino , Camundongos , Síndrome Aguda da Radiação/tratamento farmacológico , Citocinas/metabolismo , Fatores Sexuais , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico
10.
J Nanobiotechnology ; 22(1): 303, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822376

RESUMO

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients' quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.


Assuntos
Probióticos , Protetores contra Radiação , Esporos Bacterianos , Animais , Probióticos/farmacologia , Camundongos , Administração Oral , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico , Protetores contra Radiação/química , Esporos Bacterianos/efeitos da radiação , Lesões por Radiação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Intestino Delgado/microbiologia , Intestino Delgado/efeitos da radiação , Intestino Delgado/patologia , Humanos , Apoptose/efeitos dos fármacos , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos da radiação , Intestinos/microbiologia , Intestinos/patologia , Lesões Experimentais por Radiação/patologia
11.
Biochem Biophys Res Commun ; 724: 150226, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38865815

RESUMO

In patients with high-level radiation exposure, gastrointestinal injury is the main cause of death. Despite the severity of damage to the gastrointestinal tract, no specific therapeutic option is available. Tauroursodeoxycholic acid (TUDCA) is a conjugated form of ursodeoxycholic acid that suppresses endoplasmic reticulum (ER) stress and regulates various cell-signaling pathways. We investigated the effect of TUDCA premedication in alleviating intestinal damage and enhancing the survival of C57BL/6 mice administered a lethal dose (15Gy) of focal abdominal irradiation. TUDCA was administered to mice 1 h before radiation exposure, and reduced apoptosis of the jejunal crypts 12 h after irradiation. At later timepoint (3.5 days), irradiated mice manifested intestinal morphological changes that were detected via histological examination. TUDCA decreased the inflammatory cytokine levels and attenuated the decrease in serum citrulline levels after radiation exposure. Although radiation induced ER stress, TUDCA pretreatment decreased ER stress in the irradiated intestinal cells. The effect of TUDCA indicates the possibility of radiation therapy for cancer in tumor cells. TUDCA did not affect cell proliferation and apoptosis in the intestinal epithelium. TUDCA decreased the invasive ability of the CT26 metastatic colon cancer cell line. Reduced invasion after TUDCA treatment was associated with decreased matrix metalloproteinase (MMP)-7 and MMP-13 expression, which play important roles in invasion and metastasis. This study shows a potential role of TUDCA in protecting against radiation-induced intestinal damage and inhibiting tumor cell migration without any radiation and radiation therapy effect.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Camundongos Endogâmicos C57BL , Protetores contra Radiação , Ácido Tauroquenodesoxicólico , Animais , Ácido Tauroquenodesoxicólico/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos da radiação , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Protetores contra Radiação/farmacologia , Camundongos , Masculino , Intestinos/efeitos da radiação , Intestinos/efeitos dos fármacos , Intestinos/patologia , Modelos Animais de Doenças , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos da radiação , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Lesões Experimentais por Radiação/prevenção & controle , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação
12.
BMC Cardiovasc Disord ; 24(1): 323, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38918713

RESUMO

BACKGROUND: Radiotherapy is a primary local treatment for tumors, yet it may lead to complications such as radiation-induced heart disease (RIHD). Currently, there is no standardized approach for preventing RIHD. Dexmedetomidine (Dex) is reported to have cardio-protection effects, while its role in radiation-induced myocardial injury is unknown. In the current study, we aimed to evaluate the radioprotective effect of dexmedetomidine in X-ray radiation-treated mice. METHODS: 18 male mice were randomized into 3 groups: control, 16 Gy, and 16 Gy + Dex. The 16 Gy group received a single dose of 16 Gy X-ray radiation. The 16 Gy + Dex group was pretreated with dexmedetomidine (30 µg/kg, intraperitoneal injection) 30 min before X-ray radiation. The control group was treated with saline and did not receive X-ray radiation. Myocardial tissues were collected 16 weeks after X-ray radiation. Hematoxylin-eosin staining was performed for histopathological examination. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was performed to assess the state of apoptotic cells. Immunohistochemistry staining was performed to examine the expression of CD34 molecule and von Willebrand factor. Besides, western blot assay was employed for the detection of apoptosis-related proteins (BCL2 apoptosis regulator and BCL2-associated X) as well as autophagy-related proteins (microtubule-associated protein 1 light chain 3, beclin 1, and sequestosome 1). RESULTS: The findings demonstrated that 16 Gy X-ray radiation resulted in significant changes in myocardial tissues, increased myocardial apoptosis, and activated autophagy. Pretreatment with dexmedetomidine significantly protects mice against 16 Gy X-ray radiation-induced myocardial injury by inhibiting apoptosis and autophagy. CONCLUSION: In summary, our study confirmed the radioprotective effect of dexmedetomidine in mitigating cardiomyocyte apoptosis and autophagy induced by 16 Gy X-ray radiation.


Assuntos
Apoptose , Autofagia , Dexmedetomidina , Miócitos Cardíacos , Lesões Experimentais por Radiação , Animais , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/efeitos da radiação , Miócitos Cardíacos/metabolismo , Apoptose/efeitos dos fármacos , Masculino , Dexmedetomidina/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/farmacologia , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Camundongos , Proteínas Relacionadas à Autofagia/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Reguladoras de Apoptose/metabolismo
13.
Redox Biol ; 73: 103219, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38851001

RESUMO

Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage invitro and invivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice. Importantly, APN also conferred no protection from radiation to prostate cancer cells. Adipose tissue is the primary source of circulating endogenous adiponectin. However, this study shows that adipose tissue is sensitive to radiation exposure exhibiting morphological changes and persistent oxidative damage. In addition, radiation results in a significant and chronic reduction in blood APN levels from adipose tissue in mice and human prostate cancer patients exposed to pelvic irradiation. APN levels negatively correlated with bowel toxicity and overall toxicities associated with radiotherapy in prostate cancer patients. Thus, protecting, or modulating APN signaling may improve outcomes for prostate cancer patients undergoing radiotherapy.


Assuntos
Adiponectina , Fibrose , Estresse Oxidativo , Neoplasias da Próstata , Masculino , Animais , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Humanos , Camundongos , Estresse Oxidativo/efeitos da radiação , Adiponectina/metabolismo , Adiponectina/sangue , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos da radiação , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico
14.
Microbiol Res ; 286: 127821, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38941923

RESUMO

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy. In this study, we investigated the potential protective effect of Lactobacillus rhamnosus GG (LGG) on radiation-induced intestinal injury and its underlying mechanisms. Mice were assigned to a control group, a 10 Gy total abdominal irradiation (TAI) group, or a group pretreated with 108 CFU LGG for three days before TAI. Small intestine and gut microbiota were analyzed 3.5 days post-exposure. LGG intervention improved intestinal structure, reduced jejunal DNA damage, and inhibited the inflammatory cGAS/STING pathway. Furthermore, LGG reduced M1 proinflammatory macrophage and CD8+ T cell infiltration, restoring the balance between Th17 and Treg cells in the inflamed jejunum. LGG also partially restored the gut microbiota. These findings suggest the possible therapeutic radioprotective effect of probiotics LGG in alleviating radiation-induced intestinal injury by maintaining immune homeostasis and reshaping gut microbiota.


Assuntos
Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Camundongos Endogâmicos C57BL , Probióticos , Animais , Microbioma Gastrointestinal/efeitos da radiação , Camundongos , Probióticos/administração & dosagem , Lesões por Radiação/imunologia , Macrófagos/imunologia , Intestinos/microbiologia , Intestinos/efeitos da radiação , Intestinos/imunologia , Dano ao DNA , Linfócitos T CD8-Positivos/imunologia , Proteínas de Membrana/metabolismo , Linfócitos T Reguladores/imunologia , Masculino , Células Th17/imunologia , Jejuno/efeitos da radiação , Jejuno/imunologia , Jejuno/microbiologia , Protetores contra Radiação/farmacologia , Protetores contra Radiação/uso terapêutico , Lesões Experimentais por Radiação/imunologia , Lesões Experimentais por Radiação/prevenção & controle , Nucleotidiltransferases
15.
Eur J Pharm Biopharm ; 201: 114347, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38825168

RESUMO

PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.


Assuntos
Administração Cutânea , Agulhas , Polietilenoglicóis , Radiodermite , Absorção Cutânea , Pele , Superóxido Dismutase , Adesivo Transdérmico , Polietilenoglicóis/química , Animais , Superóxido Dismutase/metabolismo , Superóxido Dismutase/administração & dosagem , Pele/metabolismo , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Radiodermite/prevenção & controle , Absorção Cutânea/efeitos dos fármacos , Camundongos , Masculino , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/farmacologia , Protetores contra Radiação/farmacocinética
16.
Food Funct ; 15(13): 6900-6913, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38837182

RESUMO

Diet-derived exosome-like nanovesicles are a class of natural active substances that have similar structures and functions to mammalian exosomes. Biyang floral mushrooms and their active extracts have been found to possess radioprotective effects and to deeply explore their novel active substances, the radioprotective effects of Biyang floral mushroom-derived exosome-like nanovesicles (BFMELNs) were investigated in this study. Results showed that these surface-negatively charged vesicles possessed an ideal size and good stability against environmental changes such as temperature and gastrointestinal digestion. Furthermore, BFMELNs could effectively be taken up by HL-7702 cells and Caco-2 cells through cellular phagocytosis mediated by clathrin and dynein. Emphatically, BFMELNs with an exosome-like morphology contained RNA, proteins, lipids, polyphenols and flavonoids to exert good antioxidant and radioprotective effects in vitro. Meanwhile, BFMELNs also exhibited good radioprotective effects by restoring peripheral blood indexes, mitigating damage to organs, and regulating the redox state in mice. Collectively, BFMELNs showed promise as novel and natural radioprotective nano-agents for preventing IR-induced oxidative stress damage.


Assuntos
Exossomos , Radiação Ionizante , Protetores contra Radiação , Humanos , Animais , Camundongos , Protetores contra Radiação/farmacologia , Protetores contra Radiação/química , Exossomos/metabolismo , Células CACO-2 , Masculino , Agaricales/química , Antioxidantes/farmacologia , Antioxidantes/química , Estresse Oxidativo/efeitos dos fármacos
17.
In Vivo ; 38(4): 1636-1648, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936936

RESUMO

BACKGROUND/AIM: The small intestine is one of the organs most vulnerable to ionizing radiation (IR) damage. However, methods to protect against IR-induced intestinal injury are limited. CBLB502, a Toll-like receptor 5 (TLR5) agonist from Salmonella flagellin, exerts radioprotective effects on various tissues and organs. However, the molecular mechanisms by which CBLB502 protects against IR-induced intestinal injury remain unclear. Thus, this study aimed to elucidate the mechanisms underlying IR-induced intestinal injury and the protective effects of CBLB502 against this condition in mice. MATERIALS AND METHODS: Mice were administered 0.2 mg/kg CBLB502 before IR at different doses for different time points, and then the survival rate, body weight, hemogram, and histopathology of the mice were analyzed. RESULTS: CBLB502 reduced IR-induced intestinal injury. RNA-seq analysis revealed that different doses and durations of IR induced different regulatory patterns. CBLB502 protected against intestinal injury mainly after IR by reversing the expression of IR-induced genes and regulating immune processes and metabolic pathways. CONCLUSION: This study preliminarily describes the regulatory mechanism of IR-induced intestinal injury and the potential molecular protective mechanism of CBLB502, providing a basis for identifying the functional genes and molecular mechanisms that mediate protection against IR-induced injury.


Assuntos
Protetores contra Radiação , Animais , Camundongos , Protetores contra Radiação/farmacologia , Receptor 5 Toll-Like/agonistas , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/metabolismo , Masculino , Radiação Ionizante , Receptores Toll-Like/metabolismo , Receptores Toll-Like/agonistas , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Intestinos/efeitos da radiação , Modelos Animais de Doenças , Agonistas do Receptor Semelhante a Toll , Peptídeos
18.
Sci Rep ; 14(1): 13315, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858439

RESUMO

Exposure to high, marginally lethal doses or higher of ionizing radiation, either intentional or accidental, results in injury to various organs. Currently, there is only a limited number of safe and effective radiation countermeasures approved by US Food and Drug Administration for such injuries. These approved agents are effective for only the hematopoietic component of the acute radiation syndrome and must be administered only after the exposure event: currently, there is no FDA-approved agent that can be used prophylactically. The nutraceutical, gamma-tocotrienol (GT3) has been found to be a promising radioprotector of such exposure-related injuries, especially those of a hematopoietic nature, when tested in either rodents or nonhuman primates. We investigated the nature of injuries and the possible protective effects of GT3 within select organ systems/tissues caused by both non-lethal level (4.0 Gy), as well as potentially lethal level (5.8 Gy) of ionizing radiation, delivered as total-body or partial-body exposure. Results indicated that the most severe, dose-dependent injuries occurred within those organ systems with strong self-renewing capacities (e.g., the lymphohematopoietic and gastrointestinal systems), while in other tissues (e.g., liver, kidney, lung) endowed with less self-renewal, the pathologies noted tended to be less pronounced and less dependent on the level of exposure dose or on the applied exposure regimen. The prophylactic use of the test nutraceutical, GT3, appeared to limit the extent of irradiation-associated pathology within blood forming tissues and, to some extent, within the small intestine of the gastrointestinal tract. No distinct, global pattern of bodily protection was noted with the agent's use, although a hint of a possible radioprotective benefit was suggested not only by a lessening of apparent injury within select organ systems, but also by way of noting the lack of early onset of moribundity within select GT3-treated animals.


Assuntos
Suplementos Nutricionais , Protetores contra Radiação , Animais , Protetores contra Radiação/farmacologia , Vitamina E/farmacologia , Vitamina E/análogos & derivados , Síndrome Aguda da Radiação/prevenção & controle , Síndrome Aguda da Radiação/tratamento farmacológico , Síndrome Aguda da Radiação/patologia , Cromanos/farmacologia , Masculino , Lesões Experimentais por Radiação/prevenção & controle , Lesões Experimentais por Radiação/patologia , Macaca mulatta , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Fígado/patologia
19.
IET Nanobiotechnol ; 2024: 5538107, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863968

RESUMO

Materials and Methods: This study followed the PRISMA reporting guidelines to present the results. A comprehensive search was performed on electronic databases such as PubMed, Scopus, Web of Sciences, and Science Direct. Initially, 413 articles were retrieved. After removing duplicates and applying specific inclusion and exclusion criteria, 10 articles were finally included in this systematic review. Results: The reviewed studies showed that selenium nanoparticles had anti-inflammatory and antioxidant properties. They effectively protected the kidneys, liver, and testicles from damage. Furthermore, there was evidence of efficient radioprotection for the organs examined without significant side effects. Conclusions: This systematic review emphasizes the potential advantages of using selenium nanoparticles to prevent the negative effects of ionizing radiation. Importantly, these protective effects were achieved without causing noticeable side effects. These findings suggest the potential role of selenium nanoparticles as radioprotective agents, offering possible therapeutic applications to reduce the risks related to ionizing radiation exposure in medical imaging and radiotherapy procedures.


Assuntos
Protetores contra Radiação , Selênio , Selênio/química , Selênio/farmacologia , Protetores contra Radiação/química , Protetores contra Radiação/farmacologia , Animais , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Nanopartículas/química , Nanopartículas Metálicas/química , Lesões por Radiação/prevenção & controle
20.
ACS Appl Mater Interfaces ; 16(23): 29917-29929, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38813785

RESUMO

Radiotherapy commonly causes damage to healthy tissues, particularly radiation-induced skin injury (RISI) that affects a significant majority of patients undergoing radiotherapy. Effective treatments for RISI are lacking. This study focuses on the pathogenesis of RISI, which primarily involves oxidative stress. Excessive reactive oxygen species (ROS) generation during radiation induces damage to biological macromolecules, triggering oxidative stress and inflammation. To address this, ergothioneine (EGT), a natural and biocompatibile thiol compound with excellent antioxidant activity, is explored as a potential radiation-protective agent. By utilizing its specific transport and absorption in the skin tissue, as well as its efficient and stable clearance of radiation-induced "ROS storm", EGT is combined with sodium hyaluronate (NaHA) to develop a novel radiation protective dressing suitable for the skin. This EGT-NaHA dressing demonstrates an effective ability to scavenge free radicals and reduce oxidative stress in vitro and in vivo, reducing cellular apoptosis and inflammation. These results demonstrate the protective properties of EGT against RISI, with far-reaching implications for research and development in the field of radioprotection.


Assuntos
Bandagens , Ergotioneína , Ácido Hialurônico , Estresse Oxidativo , Protetores contra Radiação , Pele , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Ergotioneína/farmacologia , Ergotioneína/química , Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Pele/patologia , Camundongos , Humanos , Protetores contra Radiação/farmacologia , Protetores contra Radiação/química , Protetores contra Radiação/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/prevenção & controle
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA