RESUMEN
Previous studies have suggested that Lycium barbarum (L. barbarum) has a radioprotective function, although more in-depth investigation is still required. We investigated the radioprotective efficacy of extract of the fruits of L. barbarum (LBE) and its radioprotective mechanisms. Mice were exposed to 8.5 Gy, 5.5 Gy, or 6.0 Gy total body irradiation (TBI), and the survival rate, lymphocyte percentage, amount of cytokines, and viability of the irradiated cells, as well as the gut microbiome and fecal metabolomics were studied. LBE enhanced the survival of the mice exposed to 8.5 Gy γ-ray TBI or 5.5 Gy X-ray TBI. After 6.0 Gy γ-ray TBI, LBE exhibited good immunomodulatory properties, mainly characterized by the accelerated recovery of lymphocyte percentages, and the enhanced expression of immune-related cytokines. LBE reconstituted the gut microbiota of irradiated mice, increased the relative abundance of potentially beneficial genera (e.g., Turicibacter, Akkermansia), and decreased the relative abundance of potentially harmful bacterial genera (e.g., Rikenellaceae_RC9_gut_group). Beneficial regulatory effects of LBE on the host metabolites were also noted, and the major upregulated metabolites induced by LBE, such as Tetrahydrofolic acid and N-ornithyl-L-taurine, were positively correlated with the immune factor interleukin (IL)-6. In vitro, LBE also increased the vitality of rat small intestinal epithelial cells (IEC-6) after 4.0 Gy γ-ray irradiation and promoted the growth of Akkermansia muciniphila. These results confirmed a radioprotective function of LBE and indicated that the radioprotective mechanism may be due to immunomodulation and the synergistically modulating effect on the gut microbiota and related metabolites.
Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Inmunidad/efectos de los fármacos , Lycium/química , Extractos Vegetales/uso terapéutico , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Animales , Citocinas/metabolismo , Células Epiteliales/efectos de los fármacos , Heces/microbiología , Frutas/química , Inmunomodulación/efectos de los fármacos , Interleucina-6/metabolismo , Intestino Delgado/efectos de los fármacos , Recuento de Linfocitos , Masculino , Metabolómica , Ratones , Ratones Endogámicos C57BL , Traumatismos Experimentales por Radiación/metabolismo , Ratas , Análisis de Supervivencia , Irradiación Corporal TotalRESUMEN
In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co60 γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 µg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.
Asunto(s)
Fragmentos de Péptidos/farmacología , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/farmacología , Receptor Toll-Like 5/agonistas , Animales , Evaluación Preclínica de Medicamentos , Humanos , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/efectos de la radiación , Inyecciones Intramusculares , Macaca fascicularis , Masculino , Fragmentos de Péptidos/uso terapéutico , Traumatismos Experimentales por Radiación/inmunología , Protectores contra Radiación/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Transducción de Señal/efectos de la radiación , Receptor Toll-Like 5/metabolismo , Irradiación Corporal TotalRESUMEN
Nanoparticle is a microscopic particle that has been existed in a wide range of biotechnological purposes. Zinc oxide nanoparticles (ZnO-NPs) have fewer environmental hazards and have shown positive impacts in the medical field. This work aimed to observe the effects of low and high doses of ZnO-NPs on heart injury induced by ionizing radiation (IR). Animals were irradiated by 8 Gy of gamma rays and ZnO-NPs (10 and 300 mg/Kg/day) were orally delivered to rats 1 hour after irradiation. Animals were dissected on 15th day postirradiation. Data showed that the oxidative damage resulted from radiation exposure, appeared by marked increments in the malondialdehyde (MDA) content and the level and protein expression of thioredoxin-interacting protein (TXNIP) with a noticeable decline in the level and expression of thioredoxin 1 (Trx-1) and thioredoxin reductase (TrxR), as well as glutathione (GSH) level and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Moreover, radiation-induced inflammation, manifested by a noticeable elevation in the level of tumor necrotic factor-alpha (TNF-α), interleukin-18 (IL-18), and C-reactive protein (CRP). Additionally, endothelial dysfunction marked with a high level of asymmetric dimethylarginine (ADMA), total nitrite/nitrate (NOx), intercellular adhesion molecule 1 (ICAM-1), homocysteine (Hcy), creatine kinase (CK-MB), cardiac troponin-I (cTn-I), and lactate dehydrogenase (LDH). In addition, a decrease of zinc (Zn) level in the cardiac tissue was recorded. ZnO-NPs treatment (10 mg/kg) mitigated the oxidative stress and inflammation effects on the cardiovascular tissue through the positive modulations in the studied parameters. In contrast, ZnO-NPs treatment (300 mg/kg) induced cardiovascular toxicity of normal rats and elevated the deleterious effects of radiation. In conclusion, ZnO-NPs at a low dose could mitigate the adverse effects on cardiovascular tissue induced by radiation during its applications, while the high dose showed morbidity and mortality in normal and irradiated rats.
Asunto(s)
Arginina/análogos & derivados , Proteínas de Ciclo Celular/metabolismo , Rayos gamma , Corazón , Nanopartículas/química , Traumatismos Experimentales por Radiación/metabolismo , Óxido de Zinc/farmacología , Animales , Arginina/metabolismo , Biomarcadores/metabolismo , Cardiotoxicidad , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Corazón/efectos de los fármacos , Corazón/efectos de la radiación , Inflamación , Masculino , Estrés Oxidativo/efectos de los fármacos , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/prevención & control , Ratas , Óxido de Zinc/química , Óxido de Zinc/toxicidadRESUMEN
OBJECTIVE: Studying correlative changes of Th1/Th2 (Th, Helper T cells) related factor Interferon-γ (IFN-γ) and Interleukin-4 (IL-4) in the progression of radiation pneumonia (RP) rats and the efficacy of Shashen-Maidong decoction on these indexes to explore the immune mechanism of the decoction on the prevention and treatment of RP. METHODS: Male 60 Sprague-Dawley (SD) rats were randomly divided into four groups. In addition to the normal control group taking saline, the other rats were set up RP model treated with Shashen-Maidong decoction or dexamethasone (DXM), respectively. The IFN-γ and IL-4 concentrations in serum and bronchoalveolar lavage fluid (BALF) of rats were tested in the 2nd and 4th week after radiation, and the relative ratio of IFN-γ/IL-4 was calculated. RESULTS: (1) There was significant difference of serum IL-4 concentrations in group B (p<0.01) and extreme difference in groups C and D (p<0.001) compared with group A in 4th week. Compared with group D, IL-4 concentrations in group B increased significantly in both 2nd and 4th week (p<0.01). Group B had significantly decreased IFN-γ concentrations in BALF (p<0.001) compared with group D in the 4th week. And IFN-γ concentrations in BALF in group B were increased compared with group C in the 4th week (p<0.05). (2) There was no difference of the relative ratio of IFN-γ/IL-4 at each time in groups B and A for both serum and BALF, while the ratios in groups C and D in 4th week in BALF were increased (p<0.05) compared to group A. CONCLUSION: Shashen-Maidong decoction can improve the immune function of RP rats by increasing IFN-γ concentration and decreasing IL-4 concentration, possibly by increasing the relative ratio of IFN-γ/IL-4 to regulate the immune imbalance of Th1/Th2.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Interferón gamma/inmunología , Interleucina-4/inmunología , Traumatismos Experimentales por Radiación/inmunología , Neumonitis por Radiación/inmunología , Células TH1/inmunología , Células Th2/inmunología , Animales , Dexametasona/farmacología , Masculino , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Traumatismos Experimentales por Radiación/patología , Neumonitis por Radiación/tratamiento farmacológico , Neumonitis por Radiación/patología , Ratas , Ratas Sprague-Dawley , Células TH1/patología , Células Th2/patologíaRESUMEN
PURPOSE: To evaluate antioxidant effects of active vitamin D (calcitriol) against high-dose radioiodine (RAI) therapy-associated damage of lacrimal gland. MATERIALS AND METHODS: Wistar albino rats were used and divided into three groups randomly (n = 12/group). The first group was appointed as the negative control group and received no RAI or medication. The second group was appointed as the positive control group that only received 3 mCi/kg (111 MBq/kg) RAI via gastric gavage and the last group was the treatment group that received 3 mCi/kg RAI via same method and calcitriol (200 ng/kg/day) via intraperitoneal administration. Seven days after RAI administration, bilateral intraorbital (IG), extraorbital (EG) and Harderian (HG) glands were removed for the evaluations of histopathologic, tissue cytokine, total oxidant status (TOS) and total antioxidant status (TAS). RESULTS: RAI led to significant increase in tissue TOS, TNF-α, IL-6 levels and significant decrease in IL-10 and TAS levels (p < 0.05 for each). Addition of adjunctive calcitriol reversed all these parameters significantly (p < 0.05 for each).The following histopathologic parameters were seen more frequently in positive control group than the other groups: Abnormal lobular pattern, perivascular infiltration, periductal infiltration, lipofuscin-like accumulation, acinar atrophy, periductal and periacinar fibrosis in all lacrimal gland types (p < 0.05), acinar fibrosis in EG (p = 0.049), periductal fibrosis in EG and HG (p = 0.049 and 0.038, respectively), abnormal cell outlines in EG and HG (p = 0.020 and 0.011, respectively) and variation in cell size in the IG and the HG (p = 0.003 and 0.049 respectively). CONCLUSIONS: RAI caused significant oxidative stress and inflammation in lacrimal glands. Vitamin D demonstrated potent anti-inflammatory, antioxidant and radio-protective effects on lacrimal glands in histopathologic, tissue cytokine and oxidant/antioxidant level evaluations.
Asunto(s)
Antioxidantes/uso terapéutico , Radioisótopos de Yodo/toxicidad , Aparato Lagrimal/efectos de los fármacos , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Vitamina D/uso terapéutico , Animales , Citocinas/inmunología , Modelos Animales de Enfermedad , Aparato Lagrimal/inmunología , Aparato Lagrimal/patología , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/patología , Ratas WistarRESUMEN
Blackcurrants (Ribes nigrum L.) have various benefits for human health. In particular, a polysaccharide derived from blackcurrant was found to be an immunostimulating food ingredient in a mouse model. We named a polysaccharide derived from blackcurrant cassis polysaccharide (CAPS). In a previous clinical study, we reported that CAPS affects skin dehydration, demonstrating its effectiveness against skin inflammation was related to atopic dermatitis; skin inflammation caused skin dehydration. However, there are no studies regarding CAPS effectiveness against skin dehydration. The current study aimed to investigate CAPS effectiveness against skin dehydration. We further demonstrate the effect of oral administration of CAPS on skin dehydration caused by ultraviolet (UV) irradiation-induced inflammation in mice. We found that CAPS administration suppresses skin dehydration caused by UV irradiation. We also found that CAPS decreases interleukin-6 and matrix metalloproteinase transcription levels in the mouse skin. These results show that CAPS improves skin hydration in UV-irradiated mice.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Dermatitis Atópica/terapia , Carbohidratos de la Dieta/uso terapéutico , Frutas/química , Extractos Vegetales/uso terapéutico , Ribes/química , Piel/metabolismo , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Dermatitis Atópica/etiología , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/análisis , Carbohidratos de la Dieta/aislamiento & purificación , Fibras de la Dieta/administración & dosificación , Fibras de la Dieta/análisis , Fibras de la Dieta/uso terapéutico , Suplementos Dietéticos/análisis , Femenino , Regulación de la Expresión Génica/efectos de la radiación , Interleucina-6/antagonistas & inhibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinasa 13 de la Matriz/química , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Ratones Pelados , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Prebióticos/administración & dosificación , Prebióticos/análisis , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/terapia , Piel/inmunología , Piel/efectos de la radiación , Organismos Libres de Patógenos Específicos , Rayos Ultravioleta/efectos adversos , Agua/metabolismoRESUMEN
Syzygium aromaticum L., commonly named clove, is widely used in the food industry due to its antioxidant and antibacterial capabilities. However, little information is available regarding its role in resisting skin photoaging. This study investigated 50% ethanol extract of Syzygium aromaticum L. (SA) and eugenol (EO) for anti-aging effects in UVB-irradiated normal human dermal fibroblasts (NHDFs) and hairless mice. In vitro, SA and EO suppressed matrix metalloproteinase-1, 3 (MMP-1 and MMP-3) secretion as well as the activator protein 1 (AP-1) phosphorylation. SA and EO also activated nuclear erythroid 2-related factor/antioxidant-response element (Nrf2/ARE) signaling which improves the antioxidant activity and inhibited nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) expression, pro-inflammatory factors. Furthermore, SA and EO suppressed the nuclear factor of activated T cells c1 (NFATc1) which is a known activator of MMPs, cooperator transforming growth factor beta (TGF-ß) and NF-κB in Ca2+/calcineurin-regulated transcription. In vivo, SA significantly improved the levels of procollagen type I and elastin through TGF/Smad signaling. The histopathological studies found that SA reduced wrinkles. SA also increased filament aggregating protein (filaggrin), which repairs the skin barrier function and improved the skin's hydration. Altogether, SA effectively ameliorated UVB-induced photoaging. It is expected to become a promising natural product.
Asunto(s)
Suplementos Dietéticos , Copas de Floración/química , Extractos Vegetales/uso terapéutico , Traumatismos Experimentales por Radiación/terapia , Piel/efectos de la radiación , Syzygium/química , Cicatrización de Heridas , Animales , Antioxidantes/uso terapéutico , Supervivencia Celular/efectos de la radiación , Células Cultivadas , Eugenol/uso terapéutico , Proteínas Filagrina , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Masculino , Ratones Pelados , Aceites Volátiles/uso terapéutico , Estrés Oxidativo/efectos de la radiación , Fosforilación/efectos de la radiación , Procesamiento Proteico-Postraduccional/efectos de la radiación , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Distribución Aleatoria , Piel/inmunología , Piel/metabolismo , Piel/patología , Envejecimiento de la Piel/inmunología , Envejecimiento de la Piel/patología , Envejecimiento de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversosRESUMEN
INTRODUCTION: External radiotherapy is one of the main treatment modalities for a variety of malignancies. However, the lower gastrointestinal tract is sensitive to the ionizing radiation. Hyperbaric oxygen treatment (HOT) has been suggested as a viable treatment for refractory radiation colitis, but the effect of S-Methylisothiourea (SMT) in the radiation colitis have not reported. To investigate the effect of SMT, HOT and the combination of both in an acute radiation-induced enterocolitis model. METHODS: Sixty Sprague-Dawley rats were divided randomly into five equal groups. A single dose of gamma irradiation (25 Gy) was administered through the colorectal region to anesthetized rats. In the control group, we applied 2âml of saline solution intraperitoneally for five days. In the HOT group, 100-per-cent oxygen at 2.5 atm pressure was applied for five days. In the SMT group, 10âmg/kg/day of SMT was applied intraperitoneally for five days. In the HOT+SMT group, HOT and SMT were both applied in the same dosages as in the preceding two groups. At the end of five days, the rats were sacrificed and colon samples were collected for histological grading. Blood samples were collected to test forâ: tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-1ß, transforming growth factor-ß (TGF-ß) and intercellular adhesion molecule-1 (ICAM-1) mRNA. RESULTS: The TNF-α, IL-1ß, IL-10 and TGF-ß levels were reduced by SMT, HOT and HOT+SMT applications (pâ<â0.05). However ICAM-1 mRNA levels were not significantly lower (p:0.19). The microscopic scores differed significantly between the SMT, HOT and HOT+SMT groups and the control group. There was significant improvement histologically, especially in the HOT+SMT group. When we compared the weight of the rats before and after the study, weight loss was significantly lower in the SMT, HOT and HOT+SMT groups compared with the control group (pâ<â0.05). CONCLUSION: HOT and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately.
Asunto(s)
Colitis/terapia , Colon/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Oxigenoterapia Hiperbárica , Isotiuronio/análogos & derivados , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Animales , Colitis/inmunología , Colitis/patología , Colon/inmunología , Colon/patología , Femenino , Molécula 1 de Adhesión Intercelular/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/inmunología , Interleucina-10/inmunología , Interleucina-1beta/efectos de los fármacos , Interleucina-1beta/inmunología , Isotiuronio/farmacología , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/patología , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta/efectos de los fármacos , Factor de Crecimiento Transformador beta/inmunología , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Carbon ion radiation is a promising treatment for brain cancer; however, the immune system involved long-term systemic effects evoke a concern of complementary and alternative therapies in clinical treatment. To clarify radiotherapy caused fundamental changes in peripheral immune system, examinations were performed based on established models in vitro and in vivo. We found that brain-localized carbon ion radiation of neural cells induced complex changes in the peripheral blood, thymus, and spleen at one, two, and three months after its application. Atrophy, apoptosis, and abnormal T-cell distributions were observed in rats receiving a single high dose of radiation. Radiation downregulated the expression of proteins involved in T-cell development at the transcriptional level and increased the proportion of CD3âºCD4(-)CD8⺠T-cells in the thymus and the proportion of CD3âºCD4âºCD8(-) T-cells in the spleen. These data show that brain irradiation severely affects the peripheral immune system, even at relatively long times after irradiation. In addition, they provide valuable information that will implement the design of biological-based strategies that will aid brain cancer patients suffering from the long-term side effects of radiation.
Asunto(s)
Carbono , Iones , Sistema Nervioso/inmunología , Sistema Nervioso/efectos de la radiación , Traumatismos Experimentales por Radiación/inmunología , Radiación Ionizante , Animales , Apoptosis/inmunología , Apoptosis/efectos de la radiación , Biomarcadores , Encéfalo/inmunología , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/efectos de la radiación , Línea Celular , Modelos Animales de Enfermedad , Humanos , Terapia de Inmunosupresión , Activación de Linfocitos/inmunología , Activación de Linfocitos/efectos de la radiación , Masculino , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Ratas , Bazo/inmunología , Bazo/metabolismo , Bazo/patología , Bazo/efectos de la radiación , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/patología , Linfocitos T/efectos de la radiación , Timo/inmunología , Timo/patología , Timo/efectos de la radiaciónRESUMEN
We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.
Asunto(s)
Dieta , Proteínas en la Dieta/uso terapéutico , Suplementos Dietéticos , Inflamación/terapia , Traumatismos Experimentales por Radiación/terapia , Estilbenos/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Citocinas/sangre , Desoxiguanosina/orina , Proteínas en la Dieta/administración & dosificación , Proteínas en la Dieta/farmacología , Femenino , Sistema Inmunológico/citología , Sistema Inmunológico/efectos de los fármacos , Inflamación/sangre , Inflamación/etiología , Inflamación/inmunología , Recuento de Leucocitos , Metabolismo de los Lípidos , Lípidos/sangre , Neoplasias/radioterapia , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Recuento de Plaquetas , Traumatismos Experimentales por Radiación/sangre , Traumatismos Experimentales por Radiación/inmunología , Ratas Wistar , Resveratrol , Estilbenos/farmacologíaRESUMEN
The detonation of a nuclear weapon or a nuclear accident represent possible events with significant exposure to mixed neutron/γ-radiation fields. Although radiation countermeasures generally have been studied in subjects exposed to pure photons (γ or X rays), the mechanisms of injury of these low linear energy transfer (LET) radiations are different from those of high-LET radiation such as neutrons, and these differences may affect countermeasure efficacy. We compared 30-day survival in mice after varying doses of pure γ and mixed neutron/γ (mixed field) radiation (MF, Dn/Dt = 0.65), and also examined peripheral blood cells, bone marrow cell reconstitution, and cytokine expression. Mixed-field-irradiated mice displayed prolonged defects in T-cell populations compared to mice irradiated with pure γ photons. In mouse survival assays, the growth factor granulocyte colony-stimulating factor (G-CSF) was effective as a (post-irradiation) mitigator against both γ-photons and mixed-field radiation, while the thrombopoietin (TPO) mimetic ALXN4100TPO was effective only against γ irradiation. The results indicate that radiation countermeasures should be tested against radiation qualities appropriate for specific scenarios before inclusion in response plans.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Enfermedades de la Médula Ósea/prevención & control , Rayos gamma/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neutrones/efectos adversos , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Trombopoyetina/uso terapéutico , Animales , Anticuerpos Monoclonales Humanizados , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Médula Ósea/efectos de la radiación , Enfermedades de la Médula Ósea/sangre , Enfermedades de la Médula Ósea/etiología , Enfermedades de la Médula Ósea/inmunología , Citocinas/sangre , Evaluación Preclínica de Medicamentos , Filgrastim , Hematopoyesis/efectos de los fármacos , Hematopoyesis/efectos de la radiación , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/patología , Células Madre Hematopoyéticas/efectos de la radiación , Recuento de Linfocitos , Ratones , Traumatismos Experimentales por Radiación/sangre , Traumatismos Experimentales por Radiación/etiología , Traumatismos Experimentales por Radiación/inmunología , Proteínas Recombinantes/uso terapéutico , Bazo/efectos de los fármacos , Bazo/patología , Bazo/efectos de la radiación , Linfocitos T/efectos de la radiaciónRESUMEN
Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix, Cnidium officinale , and Paeonia japonica cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway.
Asunto(s)
Rayos gamma/efectos adversos , Síndromes de Inmunodeficiencia/prevención & control , Interleucina-12/fisiología , Células Asesinas Naturales/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Protectores contra Radiación/uso terapéutico , Factor de Transcripción STAT4/fisiología , Transducción de Señal/efectos de los fármacos , Células TH1/efectos de los fármacos , Irradiación Corporal Total/efectos adversos , Animales , Formación de Anticuerpos/efectos de los fármacos , Formación de Anticuerpos/efectos de la radiación , Citotoxicidad Inmunológica/efectos de los fármacos , Citotoxicidad Inmunológica/efectos de la radiación , Fraccionamiento de la Dosis de Radiación , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Femenino , Inmunización , Síndromes de Inmunodeficiencia/etiología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de la radiación , Linfocinas/metabolismo , Ratones , Ratones Endogámicos C57BL , Fosforilación/efectos de los fármacos , Extractos Vegetales/farmacología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Traumatismos Experimentales por Radiación/inmunología , Protectores contra Radiación/farmacología , Organismos Libres de Patógenos Específicos , Bazo/inmunología , Bazo/patología , Bazo/efectos de la radiación , Células TH1/metabolismo , Células TH1/efectos de la radiación , Células Th2/efectos de los fármacos , Células Th2/metabolismo , Células Th2/efectos de la radiaciónRESUMEN
The radioprotective effect of Vernonia cinerea extract was studied in balb/c mice. Whole-body irradiation of γ-rays (6 Gy) given to animals reduced the white blood cell count, bone marrow cellularity and α-esterase positive cells in control animals, which were elevated by the administration of V. cinerea extract (20 mg/kg body weight [b.wt.], intraperitoneally [i.p.]). The elevated levels of serum enzymes alkaline phosphatase (ALP), glutamate pyruvate transferases (GPT) and lipid peroxidation (LPO) after irradiation were also reduced with V. cineria extract administration. V. cinerea treatment also significantly enhanced the animal's antioxidant status by enhancing the activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) level in irradiated animals. Histopathological analysis of liver and small intestine also suggests that V. cinerea could reduce the tissue damages induced by radiation. The level of pro-inflammatory cytokines such as interleukin 1ß (IL-1ß), tumour necrosis factor α (TNF-α) and C-reactive protein (CRP) elevated after irradiation, which were significantly reduced by V. cinerea extract administration. On the other hand, the extract stimulated the production of other cytokines such as granulocyte monocyte-colony stimulating factor (GM-CSF) and interferon-γ (IFN-γ) in animals exposed to radiation. Agarose gel electrophoresis of DNA isolated from bone marrow of control animals showed heavy DNA damage, but a reduced DNA damage was seen in animals treated with V. cinerea extract. Administration of V. cinerea did not compromise the anti-neoplastic efficiency of radiation. In fact, there was a synergistic action of radiation and V. cinerea in reducing the solid tumours in mice. Methanolic extract of V. cinerea given i.p. showed a significant radioprotective activity without compromising the radiotherapeutic efficacy of radiation, indicating its possible use as an adjuvant during radiotherapy.
Asunto(s)
Tolerancia Inmunológica , Estrés Oxidativo , Extractos Vegetales/uso terapéutico , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Vernonia/química , Animales , Citocinas/inmunología , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Rayos gamma , Hematopoyesis/efectos de los fármacos , Hematopoyesis/efectos de la radiación , Tolerancia Inmunológica/efectos de los fármacos , Tolerancia Inmunológica/efectos de la radiación , Intestino Delgado/efectos de los fármacos , Intestino Delgado/efectos de la radiación , Hígado/efectos de los fármacos , Hígado/patología , Hígado/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Neoplasias/radioterapia , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Extractos Vegetales/aislamiento & purificación , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/metabolismo , Protectores contra Radiación/aislamiento & purificación , Irradiación Corporal TotalRESUMEN
Last years, the big attention is given studying of the methods promoting increase of the immune status of an organism, got under influence of extreme factors, in particular, ionas radiations. In this connection perspectivity of application of laboratory diagnostics for testing a degree of defeat of immune system and application phytoadaptogenes is proved, namely: tinctures of a Panacis ginseng, Schizandrae chinensis, an extract Elaetherococcus for correction of such conditions.
Asunto(s)
Adaptación Fisiológica/efectos de los fármacos , Adaptación Fisiológica/efectos de la radiación , Envejecimiento Prematuro/prevención & control , Extractos Vegetales/uso terapéutico , Traumatismos Experimentales por Radiación/complicaciones , Adaptación Fisiológica/inmunología , Envejecimiento Prematuro/tratamiento farmacológico , Envejecimiento Prematuro/etiología , Envejecimiento Prematuro/inmunología , Animales , Eleutherococcus/química , Cobayas , Recuento de Leucocitos , Leucocitos/efectos de los fármacos , Leucocitos/efectos de la radiación , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/efectos de la radiación , Masculino , Ratones , Panax/química , Extractos Vegetales/administración & dosificación , Traumatismos Experimentales por Radiación/sangre , Traumatismos Experimentales por Radiación/inmunología , Análisis de Supervivencia , Timo/efectos de los fármacos , Timo/efectos de la radiación , Resultado del TratamientoRESUMEN
BACKGROUND: A marine oligopeptide preparation (MOP) obtained from Chum Salmon (Oncorhynchus keta) by the method of enzymatic hydrolysis, has been found to enhance the innate and adaptive immunities through stimulation of the secretion of cytokines in mice. The current study aimed to further investigate the protective effect of MOP on radiation-induced immune suppression in mice. RESULTS: Female ICR mice (6-8 weeks old) were randomly divided into three groups, i.e. blank control, irradiation control and MOP (1.350 g kg(-1) body weight) plus irradiation-treated group. MOP significantly increased the survival rate and prolonged the survival times for 30 days after irradiation, and lessened the radiation-induced suppression of T- or B-lymphocyte proliferation, resulting in the recovery of cell-mediated and humoral immune functions. This effect may be produced by augmentation of the relative numbers of radioresistant CD(4) (+) T cells, enhancement of the level of immunostimulatory cytokine, IL-12, reduction of the level of total cellular NF-κB through the induction of IκB in spleen and inhibition of the apoptosis of splenocytes. CONCLUSION: We propose that MOP be used as an ideal adjuvant therapy to alleviate radiation-induced injuries in cancer patients.
Asunto(s)
Linfocitos B/efectos de la radiación , Rayos gamma/efectos adversos , Oligopéptidos/uso terapéutico , Oncorhynchus keta , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Protectores contra Radiación/uso terapéutico , Linfocitos T/efectos de la radiación , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Relación CD4-CD8 , Proliferación Celular/efectos de la radiación , Citocinas/sangre , Citocinas/metabolismo , Suplementos Dietéticos , Femenino , Proteínas I-kappa B/metabolismo , Tolerancia Inmunológica/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Inhibidor NF-kappaB alfa , Oligopéptidos/administración & dosificación , Traumatismos Experimentales por Radiación/sangre , Traumatismos Experimentales por Radiación/inmunología , Protectores contra Radiación/administración & dosificación , Distribución Aleatoria , Bazo/metabolismo , Bazo/patología , Bazo/efectos de la radiación , Análisis de Supervivencia , Linfocitos T/inmunología , Linfocitos T/metabolismo , Factor de Transcripción ReIA/metabolismoRESUMEN
PURPOSE: To investigate the protective effect of immune-enhanced diet (IED) on chemoradiation-induced injury of the gastrointestinal mucosa. MATERIALS AND METHODS: Forty-eight Sprague-Dawley rats were divided into control (C, n=6), irradiation (IR, n=14), fluoropyrimidine (5-FU, n=14)-treated, IR + 5-FU (n=14)-treated groups. Half of each irradiated and/or 5-FU-treated groups were previously fed with IED containing arginine, omega-3-fatty acids and RNA fragments, while the other half were fed a standard rat diet (SD) for eight days before the induction of IR or injection of 5-FU. In IR groups, whole abdominal irradiation (11 Gy) was performed with 6 MV photons. In the 5-FU groups, fluoropyrimidine (100 mg/kg) was administered intraperitoneally 30 min prior to irradiation. All animals were sacrificed on the 4th day of IR or 5-FU injection. RESULTS: Bacterial colony counts in the ceca and mesenteric lymph nodes of IED-fed rats, which have received either 5-FU and/or irradiation were significantly lower than the corresponding SD-fed groups. Morphometric results revealed that gastric, ileal and colonic injuries were less in IED-treated IR or IR + 5-FU + IED groups, as compared to SD-fed groups. However, IED did not alter DNA fragmentation ratios. CONCLUSION: Prophylactic feeding of IED has a protective effect on chemoradiation-induced gastrointestinal injury, which appears to involve the eradication of bacterial overgrowth.
Asunto(s)
Dieta , Tracto Gastrointestinal/lesiones , Tracto Gastrointestinal/efectos de la radiación , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/prevención & control , Animales , Bacterias/crecimiento & desarrollo , Bacterias/inmunología , Bacterias/efectos de la radiación , Fragmentación del ADN/efectos de la radiación , Femenino , Mucosa Gástrica/inmunología , Mucosa Gástrica/lesiones , Mucosa Gástrica/microbiología , Mucosa Gástrica/efectos de la radiación , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/patología , Mucosa Intestinal/inmunología , Mucosa Intestinal/lesiones , Mucosa Intestinal/microbiología , Mucosa Intestinal/efectos de la radiación , Masculino , Traumatismos Experimentales por Radiación/patología , RatasRESUMEN
The goji berry, Lycium barbarum, has long been recognised in traditional Chinese medicine for various therapeutic properties based on its antioxidant and immune-modulating effects. This study describes the potential for orally consumed goji berry juice to alter the photodamage induced in the skin of mice by acute solar simulated UV (SSUV) irradiation. In Skh:hr-1 hairless mice, 5% goji berry juice significantly reduced the inflammatory oedema of the sunburn reaction. Dilutions of goji berry juice between 1% and 10% dose-dependently protected against SSUV-induced immunosuppression, and against suppression induced by the mediator, cis-urocanic acid, measured by the contact hypersensitivity reaction. The immune protection could not be ascribed to either the minor excipients in the goji juice, pear and apple juice, nor the vitamin C content, nor the preservative, and appeared to be a property of the goji berry itself. Antioxidant activity in the skin was demonstrated by the significant protection by 5% goji juice against lipid peroxidation induced by UVA radiation. Furthermore, two known inducible endogenous skin antioxidants, haem oxygenase-1 and metallothionein, were found to be involved in the photoimmune protection. The results suggest that consumption of this juice could provide additional photoprotection for susceptible humans.
Asunto(s)
Antioxidantes/farmacología , Bebidas , Ingestión de Líquidos , Lycium/química , Traumatismos Experimentales por Radiación/prevención & control , Enfermedades de la Piel/prevención & control , Rayos Ultravioleta/efectos adversos , Animales , Antioxidantes/uso terapéutico , Edema/complicaciones , Edema/dietoterapia , Edema/inmunología , Femenino , Hemo-Oxigenasa 1/metabolismo , Hipersensibilidad/inmunología , Terapia de Inmunosupresión , Inflamación/complicaciones , Inflamación/dietoterapia , Inflamación/inmunología , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/efectos de la radiación , Metalotioneína/metabolismo , Ratones , Ratones Pelados , Ácidos Oléicos/inmunología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/metabolismo , Enfermedades de la Piel/etiología , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/metabolismo , Quemadura Solar/complicaciones , Quemadura Solar/dietoterapia , Quemadura Solar/inmunologíaRESUMEN
BACKGROUND AND AIM: Sixty male Wistar rats, divided into 4 groups, 15 each, were designed as I-control rats, II-rats orally intubated with Nigella sativa oil (1 ml/kg b.wt./day) for 5 days/week, III-whole body gamma irradiated rats with the estimated LD50/30 (4 Gray) and IV-rats daily intubated with Nigella sativa oil then subjected to whole body gamma irradiation, to investigate the radioprotective potential of Nigella crude oil against hemopoietic adverse effects of gamma irradiation. RESULTS: Irradiation resulted in significant reduction in hemolysin antibodies titers and delayed type hypersensitivity reaction of irradiated rats, in addition to significant leukopenia and significant decrease in plasma total protein and globulin concentrations and depletion of lymphoid follicles of spleen and thymus gland. Furthermore, there was a significant increase in malondialdehyde concentration with a significant decrease in plasma glutathione peroxidase, catalase and erythrocyte superoxide dismutase activities were recorded. Oral administration of Nigella sativa oil before irradiation considerably normalized all the above-mentioned criteria; and produced significant regeneration in spleen and thymus lymphoid follicles. CONCLUSION: Our results strongly recommend Nigella sativa oil as a promising natural radioprotective agent against immunosuppressive and oxidative effects of ionizing radiation.
Asunto(s)
Nigella sativa/química , Aceites de Plantas/uso terapéutico , Traumatismos Experimentales por Radiación , Protectores contra Radiación/uso terapéutico , Administración Oral , Animales , Antioxidantes/metabolismo , Proteínas Sanguíneas/metabolismo , Células Cultivadas , Relación Dosis-Respuesta en la Radiación , Recuento de Eritrocitos , Eritrocitos/efectos de los fármacos , Eritrocitos/enzimología , Eritrocitos/inmunología , Cobayas , Hemólisis/efectos de los fármacos , Hemólisis/efectos de la radiación , Tolerancia Inmunológica/efectos de los fármacos , Tolerancia Inmunológica/efectos de la radiación , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/efectos de la radiación , Inmunidad Humoral/efectos de los fármacos , Inmunidad Humoral/efectos de la radiación , Recuento de Leucocitos , Leucopenia/sangre , Leucopenia/etiología , Leucopenia/prevención & control , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/efectos de la radiación , Masculino , Aceites de Plantas/administración & dosificación , Aceites de Plantas/aislamiento & purificación , Traumatismos Experimentales por Radiación/sangre , Traumatismos Experimentales por Radiación/inmunología , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/administración & dosificación , Protectores contra Radiación/aislamiento & purificación , Ratas , Ratas Wistar , Semillas/química , Ovinos , Bazo/efectos de los fármacos , Bazo/enzimología , Bazo/efectos de la radiación , Timo/efectos de los fármacos , Timo/enzimología , Timo/efectos de la radiación , Irradiación Corporal TotalRESUMEN
Recombinant human interleukine-1beta (betaleukune) of Institute of especially pure biopreparation production had been examined as a treatment means at acute radiation disease of severe degree at dogs. Dogs were irradiated totally in doses above the LD95/45. Betaleukine had been administered s/c twice in day in 15 min - 2 h after irradiation. All the dogs, including control ones, received in acute period 8-24/26 days after irradiation antibiotics ampicillin and gentamycin i/m. Betaleukine increased 45 day-survival by 37% at 4 Gy and by 25% at 4.4 Gy. The effect correlated with more high level of nadir and more early beginning the leucocyte number restoration. We observed the regularity at all the dogs that received betaleukine as survived as died, but in the latter case in a lesser degree certainly. Besides the noticed character of leucocytes kinetics had been repeated at all the blood cell types but in the different degree. It had been concluded on the base of these observations that betaleukine acts on hemopoietic stem cells preferentially. The effect is in preventing death of a stem cells part, or in stimulating survived stem cells proliferation, or in both together. Betaleukin can be regarded as a suitable means of urgent pathogenic therapy at radiation accidents.
Asunto(s)
Síndrome de Radiación Aguda/tratamiento farmacológico , Interleucina-1beta/uso terapéutico , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Síndrome de Radiación Aguda/inmunología , Ampicilina/administración & dosificación , Animales , Antibacterianos/administración & dosificación , Perros , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Femenino , Gentamicinas/administración & dosificación , Humanos , Inyecciones Intramusculares , Inyecciones Subcutáneas , Interleucina-1beta/administración & dosificación , Recuento de Leucocitos , Masculino , Traumatismos Experimentales por Radiación/inmunología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéuticoRESUMEN
A single dose of 6 Gy irradiation significantly reduced the total WBC count while in herbal formulation (AC II) treated groups it was found to be significantly increased. Similarly bone marrow cellularity and alpha-esterase positive cells, which were lowered by radiation, were partly restored in AC II treated groups. The data indicate that AC II can overcome the immunosuppression produced by irradiation.