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1.
J Altern Complement Med ; 27(10): 824-831, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34161146

RESUMO

Background: Thoracic radiotherapy is complicated by acute radiation-induced adverse events such as radiation pneumonitis (RP) and radiation esophagitis (RE). Based on preclinical work and a randomized pilot trial from our laboratory, this single-arm phase II trial investigated administering flaxseed as a radioprotector in patients receiving definitive chemoradiation for nonsmall cell lung cancer (NSCLC). Methods: Between June 2015 and February 2018, 33 patients with locally advanced or metastatic NSCLC with planned definitive chemoradiation were enrolled. Finely-ground Linum usitatissimum L. (Linaceae; flaxseed or linseed) in 40-g packets were provided for daily consumption in any patient-desired formulation 1 week before radiotherapy and throughout radiotherapy as tolerated. The primary outcomes were overall adverse events, with particular focus on Grade ≥3 RP, and flaxseed tolerability. Adverse events were graded according to CTCAE v4.0. Results: Of the 33 patients enrolled, 5 patients (15%) did not receive chemoradiation, 4 (12%) withdrew promptly after enrollment, 4 (12%) did not return a flaxseed consumption log, and 1 patient had irritable bowel syndrome (3%). The remaining 19 patients (57%) had chemoradiation and flaxseed ingestion with a mean completion and standard deviation of the intended flaxseed course of 62% ± 8.3%. Nine (50%) of these 19 patients reported difficulties with flaxseed consumption, citing nausea, constipation, odynophagia, or poor taste or texture. One patient (5%), with unverifiable flaxseed consumption, developed Grade 3 RP. There were no cases of Grade 2 RP. Six patients (32%) developed Grade 2 RE, but no patients developed Grade ≥3 RE. Median overall and progression-free survival were 31 and 12 months, respectively. Conclusions: Despite the low incidence of acute radiation-induced complications reported, significant treatment-related gastrointestinal toxicities and subsequently low flaxseed tolerability inhibit accurate determination of flaxseed effect in patients receiving concurrent thoracic chemoradiation. Thus, further investigations should focus on optimizing flaxseed formulation for improved tolerability and evaluation. ClinicalTrials.gov ID: NCT02475330.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Linho , Neoplasias Pulmonares , Lesões por Radiação , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimiorradioterapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia
2.
Cancer Prev Res (Phila) ; 11(1): 27-37, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29074535

RESUMO

Flaxseed consumption is associated with reduced oxidative stress and inflammation in lung injury models and has shown anticancer effects for breast and prostate tissues. However, the chemopreventive potential of flaxseed remains unexplored for lung cancer. In this study, we investigated the effect of flaxseed on tobacco smoke carcinogen (NNK)-induced lung tumorigenesis in an A/J mouse model. Mice exposed to NNK were fed a control diet or a 10% flaxseed-supplemented diet for 26 weeks. Flaxseed-fed mice showed reduced lung tumor incidence (78%) and multiplicity, with an average of 2.7 ± 2.3 surface lung tumor nodules and 1.0 ± 0.9 H&E cross-section nodules per lung compared with the control group, which had 100% tumor incidence and an average of 10.2 ± 5.7 surface lung tumor nodules and 3.9 ± 2.6 H&E cross-section nodules per lung. Furthermore, flaxseed-fed mice had a lower incidence of adenocarcinomas compared with control-fed mice. Western blotting performed on normal lung tissues showed flaxseed suppressed phosphorylation (activation) of p-AKT, p-ERK, and p-JNK kinases. RNA-Seq data obtained from normal lung and lung tumors of control and flaxseed-fed mice suggested that flaxseed intake resulted in differential expression of genes involved in inflammation-mediated cytokine signaling (IL1, 6, 8, 9, and 12α), xenobiotic metabolism (several CYPs, GSTs, and UGTs), and signaling pathways (AKT and MAPK) involved in tumor cell proliferation. Together, our results indicate that dietary flaxseed supplementation may be an effective chemoprevention strategy for chemically induced lung carcinogenesis by altering signaling pathways, inflammation, and oxidative stress. Cancer Prev Res; 11(1); 27-37. ©2017 AACR.


Assuntos
Carcinogênese/efeitos dos fármacos , Carcinógenos/toxicidade , Citocinas/metabolismo , Linho/química , Mediadores da Inflamação/metabolismo , Neoplasias Pulmonares/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Anticarcinógenos/farmacologia , Benzo(a)pireno/toxicidade , Carcinogênese/metabolismo , Carcinogênese/patologia , Citocromo P-450 CYP1A1/metabolismo , Citocinas/genética , Glucuronosiltransferase/metabolismo , Glutationa Transferase/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/metabolismo , Masculino , Desintoxicação Metabólica Fase II , Camundongos , Camundongos Endogâmicos A , Nitrosaminas/toxicidade , Sementes/química
3.
Carcinogenesis ; 37(2): 177-87, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26678224

RESUMO

Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2(+/mu) mice. Mice (n = 16-17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 µg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL-1ß, IL-6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM.


Assuntos
Asbesto Crocidolita/toxicidade , Butileno Glicóis/administração & dosagem , Glucosídeos/administração & dosagem , Inflamação/patologia , Lignanas/administração & dosagem , Peritônio/patologia , Animais , Antioxidantes/farmacologia , Cromatografia Líquida , Dieta , Suplementos Nutricionais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Linho , Mesotelioma/patologia , Camundongos , Camundongos Mutantes , Estresse Oxidativo/efeitos dos fármacos , Lavagem Peritoneal , Peritônio/efeitos dos fármacos , Lesões Pré-Cancerosas/tratamento farmacológico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sementes , Espectrometria de Massas em Tandem , Transcriptoma
4.
Int J Mol Sci ; 17(1)2015 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-26703588

RESUMO

Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS) has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed's protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG). SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR)-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure.


Assuntos
Antioxidantes/farmacologia , Butileno Glicóis/farmacologia , Dano ao DNA , Células Endoteliais/efeitos dos fármacos , Linho/química , Raios gama , Glucosídeos/farmacologia , Pulmão/citologia , Extratos Vegetais/farmacologia , Animais , Morte Celular , Células Cultivadas , Células Endoteliais/metabolismo , Células Endoteliais/efeitos da radiação , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo
5.
BMC Complement Altern Med ; 15: 148, 2015 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-25963404

RESUMO

BACKGROUND: Cystic fibrosis (CF) leads to advanced lung disease despite aggressive care. Persistent inflammation and oxidative stress contribute to exacerbations and disease progression. Flaxseed (FS), a dietary botanical supplement with high fiber, lignan phenolics, and omega-3 fatty acids has anti-inflammatory and antioxidant properties in murine models of acute and chronic lung injury. This pilot study was designed to determine whether CF patients could tolerate FS, evaluate circulating FS metabolites, and study biomarkers of lung damage, as a prelude to studying clinical outcomes. METHODS: 10 CF patients and 5 healthy volunteers consumed 40 g of FS daily for 4 weeks with safety and tolerability being assessed. Urine was evaluated for systemic oxidative stress and plasma for FS metabolites (enterolignans) and cytokine levels. Buccal swabs were analyzed for gene expression of Nrf2-regulated antioxidant enzymes including Heme Oxygenase-1 (HO-1) and NAD(P)H Quinone Oxidoreductase 1 (NQO1). RESULTS: All subjects completed the study without serious adverse events. Plasma levels of enterolignans were detectable in both healthy controls and CF volunteers. CF patients were stratified based on plasma enterolignan levels after 2 weeks of FS administration into high- (174 to 535 nM ED and 232 to 1841 nM EL) and low- (0 to 32 nM ED and 0 to 40 nM EL) plasma lignan cohorts. The low enterolignan level cohort experienced a statistically significant drop in urinary inflammatory IsoP and plasma TNFα levels, while demonstrating higher average NQO1 mRNA levels in buccal epithelium compared to high-lignan patients. CONCLUSIONS: This pilot study demonstrated that FS is tolerated by CF patients. FS metabolites could be detected in the plasma. Future studies will assess appropriate dosing and target populations for FS, while exploring clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02014181 .


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Fibrose Cística/tratamento farmacológico , Linho/química , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Adolescente , Adulto , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Fibrose Cística/metabolismo , Fibrose Cística/patologia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Feminino , Heme Oxigenase-1/metabolismo , Humanos , Inflamação/metabolismo , Lignanas/farmacologia , Lignanas/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Pneumopatias/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Fenóis/farmacologia , Projetos Piloto , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes/química
6.
Cancer Biol Ther ; 15(7): 930-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24755684

RESUMO

INTRODUCTION: Dietary flaxseed (FS) displays antioxidant and anti-inflammatory properties in preclinical models of lung disease including radiation-induced pneumonopathy, however the mechanisms of lung radioprotection are incompletely understood. MicroRNAs (miRNAs) are short oligonucleotides that act as important posttranscriptional regulators of diverse networks including inflammatory response networks. Responses of miRNA profiles to diet and radiation exposure have been reported, but the potential contribution of miRNAs to diet-related radioprotection has never been tested. METHODS: In this exploratory pilot study, mice were fed 10% FS or a 0% FS isocaloric control diet and exposed to a single-fraction 13.5 Gy thoracic X-ray radiation treatment (XRT). Lung RNA was extracted 48 h post-XRT and small RNAs profiled by OpenArray. RESULTS: FS significantly modulated expression of multiple miRNAs, including 7 with P<0.001. miR-150 was downregulated approximately 2.9-fold in the FS groups and is disproportionately integrated into immune response-related networks. Although few miRNAs were significantly changed by radiation, interaction between diet and radiation was observed. For example, miR-29c was greatly downregulated in the FS/Control group (10- to 50-fold) but slightly upregulated in the FS/radiation group. Compared with FS/control, the FS/radiation group experienced a 50% decrease of the p53-responsive miR-34a, which regulates senescence- and apoptosis-related factors. CONCLUSIONS: FS induced significant changes in lung miRNA profile suggesting that modulation of small RNA by dietary supplements may represent a novel strategy to prevent adverse side-effects of thoracic radiotherapy. This pilot study provides insight into a potential mechanism of flaxseed's radioprotection and provides a useful model-system to further explore and optimize such small RNA-based therapies.


Assuntos
Linho , Pulmão/efeitos da radiação , MicroRNAs/metabolismo , Sementes , Animais , Dieta , Pulmão/imunologia , Pulmão/metabolismo , Camundongos , Fitoterapia , Projetos Piloto
7.
BMC Cancer ; 13: 179, 2013 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-23557217

RESUMO

BACKGROUND: Wholegrain flaxseed (FS), and its lignan component (FLC) consisting mainly of secoisolariciresinol diglucoside (SDG), have potent lung radioprotective properties while not abrogating the efficacy of radiotherapy. However, while the whole grain was recently shown to also have potent mitigating properties in a thoracic radiation pneumonopathy model, the bioactive component in the grain responsible for the mitigation of lung damage was never identified. Lungs may be exposed to radiation therapeutically for thoracic malignancies or incidentally following detonation of a radiological dispersion device. This could potentially lead to pulmonary inflammation, oxidative tissue injury, and fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in a mouse model of radiation pneumonopathy. METHODS: We evaluated FLC-supplemented diets containing SDG lignan levels comparable to those in 10% and 20% whole grain diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC) were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4 months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and oxidative damage levels, and survival. RESULTS: FLC significantly mitigated radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7% survival 4 months post-XRT compared to 60-73.3% survival in mice fed 10%-20% FLC initiated 24-72 hours post-XRT. FLC also mitigated radiation-induced lung fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased fibrosis as compared to mice fed control diet while the corresponding TGF-beta1 levels detected immunohistochemically were also decreased. Additionally, 10-20% FLC initiated at any time point post radiation exposure, mitigated radiation-induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly, neutrophilic and overall inflammatory cell infiltrate in airways and levels of nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively) were also mitigated by the lignan diet. CONCLUSIONS: Dietary FLC given early post-XRT mitigated radiation effects by decreasing inflammation, lung injury and eventual fibrosis while improving survival. FLC may be a useful agent, mitigating adverse effects of radiation in individuals exposed to incidental radiation, inhaled radioisotopes or even after the initiation of radiation therapy to treat malignancy.


Assuntos
Butileno Glicóis/administração & dosagem , Citocinas/metabolismo , Linho , Glucosídeos/administração & dosagem , Lesão Pulmonar/prevenção & controle , Fitoterapia , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/administração & dosagem , Sementes , Ração Animal , Animais , Líquido da Lavagem Broncoalveolar , Feminino , Fibrose/etiologia , Fibrose/prevenção & controle , Estimativa de Kaplan-Meier , Lignanas/administração & dosagem , Pulmão/metabolismo , Pulmão/patologia , Pulmão/efeitos da radiação , Lesão Pulmonar/complicações , Lesão Pulmonar/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos , Oxigênio/sangue , Lesões Experimentais por Radiação/complicações , Lesões Experimentais por Radiação/metabolismo , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/patologia , Taxa de Sobrevida , Fatores de Tempo , Fator de Crescimento Transformador beta1/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
8.
BMC Complement Altern Med ; 12: 47, 2012 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-22520446

RESUMO

BACKGROUND: Flaxseed (FS), a nutritional supplement consisting mainly of omega-3 fatty acids and lignan phenolics has potent anti-inflammatory, anti-fibrotic and antioxidant properties. The usefulness of flaxseed as an alternative and complimentary treatment option has been known since ancient times. We have shown that dietary FS supplementation ameliorates oxidative stress and inflammation in experimental models of acute and chronic lung injury in mice resulting from diverse toxicants. The development of lung tissue damage in response to direct or indirect oxidant stress is a complex process, associated with changes in expression levels of a number of genes. We therefore postulated that flaxseed might modulate gene expression of vital signaling pathways, thus interfering with the development of tissue injury. METHODS: We evaluated gene expression in lungs of flaxseed-fed (10%FS) mice under unchallenged, control conditions. We reasoned that array technology would provide a powerful tool for studying the mechanisms behind this response and aid the evaluation of dietary flaxseed intervention with a focus on toxicologically relevant molecular gene targets. Gene expression levels in lung tissues were analyzed using a large-scale array whereby 28,800 genes were evaluated. RESULTS: 3,713 genes (12.8%) were significantly (p < 0.05) differentially expressed, of which 2,088 had a >1.5-fold change. Genes affected by FS include those in protective pathways such as Phase I and Phase II. CONCLUSIONS: The array studies have provided information on how FS modulates gene expression in lung and how they might be related to protective mechanisms. In addition, our study has confirmed that flaxseed is a nutritional supplement with potentially useful therapeutic applications in complementary and alternative (CAM) medicine especially in relation to treatment of lung disease.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Linho/química , Pneumopatias , Pulmão/efeitos dos fármacos , Preparações de Plantas/farmacologia , Transcriptoma , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Perfilação da Expressão Gênica/métodos , Lignanas/farmacologia , Lignanas/uso terapêutico , Pulmão/metabolismo , Pneumopatias/tratamento farmacológico , Pneumopatias/genética , Pneumopatias/metabolismo , Camundongos , Fenóis/farmacologia , Fenóis/uso terapêutico , Fitoterapia , Preparações de Plantas/uso terapêutico , Sementes/química , Transdução de Sinais/genética
9.
BMC Cancer ; 11: 269, 2011 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-21702963

RESUMO

BACKGROUND: Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. METHODS: We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n = 15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. RESULTS: Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 µg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 µg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease of specific inflammatory cytokines in FS-fed mice. CONCLUSIONS: Dietary FS given post-XRT mitigates radiation effects by decreasing pulmonary fibrosis, inflammation, cytokine secretion and lung damage while enhancing mouse survival. Dietary supplementation of FS may be a useful adjuvant treatment mitigating adverse effects of radiation in individuals exposed to inhaled radioisotopes or incidental radiation.


Assuntos
Linho , Pulmão/efeitos da radiação , Fitoterapia , Preparações de Plantas/uso terapêutico , Pneumonite por Radiação/dietoterapia , Protetores contra Radiação/uso terapêutico , Radioterapia/efeitos adversos , Sementes , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Líquido da Lavagem Broncoalveolar/química , Caquexia/dietoterapia , Caquexia/etiologia , Caquexia/prevenção & controle , Citocinas/análise , Dieta , Avaliação Pré-Clínica de Medicamentos , Feminino , Lignanas/sangue , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Oxigênio/sangue , Preparações de Plantas/administração & dosagem , Fibrose Pulmonar/dietoterapia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/prevenção & controle , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/prevenção & controle , Protetores contra Radiação/administração & dosagem , Distribuição Aleatória , Redução de Peso
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