Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/001300000w2z0 |
Texto Completo: | http://repositorio.ufsm.br/handle/1/17985 |
Resumo: | The ionizing radiation exposure is able to affect the organic functions. The acute exposure produce several side effects as immunosuppression, gastrointestinal diseases, dermatitis and cardiac damage. Fractionated and localized exposure used for cancer therapy can be produced systemic side effects as anorexia and tissue necrosis. The present thesis shows two the results of two different models of radiobiology. The aim of the first study was to evaluate the radiomodifier effect in heart of black grape juice (BGJ) by animal model of acute radiation syndrome. Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source and two groups were sham-irradiated. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation. After euthanasia, the blood was collected for lactate dehydrogenase (LDH) quantification on serum and the hearts were excised and homogenized for lipid peroxidation measurement. High concentration of metabolites from lipid peroxidation in heart determined by reactive thiobarbituric acid reactive substances assay (TBARS), and high LDH level on serum were found only in gamma-irradiated group treated with placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD) analysis, which showed resveratrol (31.28 ± 0.04 mg/L) as the majority compound. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier. The second study investigated the secondary effects of fractionated whole brain irradiation (WBI). Radiotherapy is used for brain tumour treatment. WBI causes side effects such as neurocognitive impairments, anorexia and osteorradionecrosis. We used the BGJ as countermeasure to the side effects of WBI. Forty rats were exposed to 8 sessions of fractionated WBI. The total dose absorbed was 32 Gy. Forty rats were exposed to 8 sessions of fractionated WBI. The total dose absorbed was 32 Gy. The animals were divided into 4 groups equals to the studied groups in the first experiment. The rats received the BGJ or glucose and fructose solution 4 days before, during, and 4 days after WBI. Body weight, food and water consumption were measured during the experiment. The blood was collected 2 months after WBI and the mandibles were collected for morphometric and histological analysis. The irradiated and BGJ suplemented rats lost less weight than irradiated control rats (RG) in some days of WBI sessions, indicating a protective effect of BGJ. In some days, RJ rats ingested more food and water then RG rats. After WBI, all rats grew until day 61. Irradiated animals started losing weight again compared with controls as a consequence of mandibular osteoradionecrosis (ORN). Measurements performed on mandible showed that RG animals lost weight due to masticatory hypofunction. At microscopic level, osteoclastic activity and inflammation were apparent in mandibles of RG rats. Nevertheless, although BGJ did not completely restore the alterations induced by WBI, this antioxidant-rich beverage can be used to attenuate side effects of brain irradiation. In general, the BGJ offer protection to side effects induced by radiation in rats. |
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Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologiaRadiobiologiaSuco de uvaDano cardíacoEfeitos colaterais da irradiação fracionadaRadiobiologyBlack grape juiceHeart damageSecondary effect of whole brain irradiationCNPQ::CIENCIAS DA SAUDE::FARMACIAThe ionizing radiation exposure is able to affect the organic functions. The acute exposure produce several side effects as immunosuppression, gastrointestinal diseases, dermatitis and cardiac damage. Fractionated and localized exposure used for cancer therapy can be produced systemic side effects as anorexia and tissue necrosis. The present thesis shows two the results of two different models of radiobiology. The aim of the first study was to evaluate the radiomodifier effect in heart of black grape juice (BGJ) by animal model of acute radiation syndrome. Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source and two groups were sham-irradiated. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation. After euthanasia, the blood was collected for lactate dehydrogenase (LDH) quantification on serum and the hearts were excised and homogenized for lipid peroxidation measurement. High concentration of metabolites from lipid peroxidation in heart determined by reactive thiobarbituric acid reactive substances assay (TBARS), and high LDH level on serum were found only in gamma-irradiated group treated with placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD) analysis, which showed resveratrol (31.28 ± 0.04 mg/L) as the majority compound. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier. The second study investigated the secondary effects of fractionated whole brain irradiation (WBI). Radiotherapy is used for brain tumour treatment. WBI causes side effects such as neurocognitive impairments, anorexia and osteorradionecrosis. We used the BGJ as countermeasure to the side effects of WBI. Forty rats were exposed to 8 sessions of fractionated WBI. The total dose absorbed was 32 Gy. Forty rats were exposed to 8 sessions of fractionated WBI. The total dose absorbed was 32 Gy. The animals were divided into 4 groups equals to the studied groups in the first experiment. The rats received the BGJ or glucose and fructose solution 4 days before, during, and 4 days after WBI. Body weight, food and water consumption were measured during the experiment. The blood was collected 2 months after WBI and the mandibles were collected for morphometric and histological analysis. The irradiated and BGJ suplemented rats lost less weight than irradiated control rats (RG) in some days of WBI sessions, indicating a protective effect of BGJ. In some days, RJ rats ingested more food and water then RG rats. After WBI, all rats grew until day 61. Irradiated animals started losing weight again compared with controls as a consequence of mandibular osteoradionecrosis (ORN). Measurements performed on mandible showed that RG animals lost weight due to masticatory hypofunction. At microscopic level, osteoclastic activity and inflammation were apparent in mandibles of RG rats. Nevertheless, although BGJ did not completely restore the alterations induced by WBI, this antioxidant-rich beverage can be used to attenuate side effects of brain irradiation. In general, the BGJ offer protection to side effects induced by radiation in rats.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA radiação ionizante tanto em doses altas e exposição aguda ou em doses fracionadas afeta as funções orgânicas. A exposição aguda pode causar uma série de efeitos secundários como imunodepressão, alterações gastrointestinais, dermatite e dano cardíaco. Já a exposição fracionada que ocorre em pacientes oncológicos além causar efeitos na região afetada pelo câncer, pode causar uma alguns efeitos sistêmicos como anorexia e necrose tecidual. A presente tese mostra o resultado de dois modelos experimentais de Radiobiologia. O objetivo do primeiro estudo foi avaliar o efeito radiomodificador do suco de uva orgânico (SUO) no coração em modelo animal de síndrome aguda da radiação (SAR). Os 20 ratos Wistar utilizados no experimento foram divididos em 4 grupos, sendo que dois destes foram irradiados com radiação gama por meio de uma fonte de Co-60 e os outros dois grupos cumpriram o protocolo sem serem irradiados. Os animais (ratos Wistar machos) foram suplementados com SUO ou solução de glicose e frutose (2 mL/dia) administrado via intragástrica uma semana antes e 4 dias após a exposição de corpo inteiro aos raios gama. Após a eutanásia, o sangue foi coletado para a quantificação da enzima lactato desidrogenase (LDH) e o coração foi excisado e homogeneizado para a determinação da peroxidação lipídica (LPO). Concentrações elevadas dos metabólitos da LPO no coração foram determinadas pelo ensaio das substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis elevados de LDH no soro foram encontrados apenas no grupo de ratos irradiados e suplementados com placebo, principalmente nas primeiras 24h. O suco atenuou a elevação desta enzima no soro. A análise fitoquímica do SUO foi realizada por meio da determinação de compostos fenólicos totais, flavonoides e taninos. A cromatografia líquida de alta eficiência (CLAE) mostrou que o composto majoritário no SUO é o resveratrol (31.28 ± 0.04 mg/L). Os resultados deste estudo sugerem que o SUO é forte candidato a ser um radiomodicador positvo, pois, o SUO atenuou o dano oxidativo causado no coração pela radiação. O segundo estudo analisou o efeitos secundários da irrradiação cranial fracionada em simulação à radioterapia, que é utilizada para o tratamento de tumores cerebrais. No entanto, a radiação cranial fracionada pode causar efeitos colaterais como déficits neurocognitivos, anorexia e osteorradionecrose. O SUO foi usado como medida preventiva contra os efeitos colaterais da irradiação. Os animais foram expostos a 8 sessões de irradiação cranial, totalizando 32 Gy de dose absorvida. Os animais foram divididos em 4 grupos, idênticos ao experimento anterior. Os animais receberam o SUO ou a solução de glicose e frutose 4 dias antes, durante e 4 dias após a irradiação. O peso corporal e o consumo de comida e bebida foram mensurados ao longo do protocolo experimental. O sangue foi coletado 2 meses após a irradiação e a as mandíbulas foram dissecadas para a realização de análises morfométricas e histológicas. Os ratos do grupo irradiado e trato com o suco (RJ) perderam menos peso corporal quando comparados com os animais do grupo controle irradiado (RG). O grupo RJ ingeriu mais comida e bebida que o RG. Após a irradiação todos os animais cresceram até o 61º dia. Entretanto, a partir deste momento os animais irradiados começaram a perder peso em comparação aos controles. A perda de peso foi relacionada à osteorradionecrose de mandíbula. Medidas realizadas na mandíbula mostram que os animais do grupo RG perderam peso devido a uma hipofunção mastigatória. A microscopia revelou elevada atividade osteoclástica e processo inflamatório nas mandíbulas dos ratos irradiados. O SUO também aumentou a contagem leucócitos e glóbulos vermelhos no grupo irradiado e suplementado com suco. Embora, o suco não tenha restaurado completamente as alterações induzidas pela irradiação cranial, essa bebida rica em antioxidante pode ser indicada para utilização com vistas a atenuação dos efeitos secundários da irradiação cranial. De modo geral os resultados sugerem benefício líquido para os animais quando da ingestão do SUO como agente radiomodificador positivo para exposição à radiação ionizante.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeBauermann, Liliane de Freitashttp://lattes.cnpq.br/5849925846135968Andrade, Edson Ramos dehttp://lattes.cnpq.br/8133561470052522Augusti, Paula Rossinihttp://lattes.cnpq.br/5389076387673136Lopes, Gilberti Helena Hübscherhttp://lattes.cnpq.br/1172295109796807Brasil, Carla Cristina Bauermannhttp://lattes.cnpq.br/5065412932315572Freitas, Robson Borba de2019-08-21T20:12:01Z2019-08-21T20:12:01Z2015-12-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/17985ark:/26339/001300000w2z0porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2019-08-22T06:02:23Zoai:repositorio.ufsm.br:1/17985Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-08-22T06:02:23Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia |
title |
Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia |
spellingShingle |
Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia Freitas, Robson Borba de Radiobiologia Suco de uva Dano cardíaco Efeitos colaterais da irradiação fracionada Radiobiology Black grape juice Heart damage Secondary effect of whole brain irradiation CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia |
title_full |
Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia |
title_fullStr |
Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia |
title_full_unstemmed |
Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia |
title_sort |
Avaliação do efeito do suco de uva orgânico como radiomodificador em modelos experimentais de radiobiologia |
author |
Freitas, Robson Borba de |
author_facet |
Freitas, Robson Borba de |
author_role |
author |
dc.contributor.none.fl_str_mv |
Bauermann, Liliane de Freitas http://lattes.cnpq.br/5849925846135968 Andrade, Edson Ramos de http://lattes.cnpq.br/8133561470052522 Augusti, Paula Rossini http://lattes.cnpq.br/5389076387673136 Lopes, Gilberti Helena Hübscher http://lattes.cnpq.br/1172295109796807 Brasil, Carla Cristina Bauermann http://lattes.cnpq.br/5065412932315572 |
dc.contributor.author.fl_str_mv |
Freitas, Robson Borba de |
dc.subject.por.fl_str_mv |
Radiobiologia Suco de uva Dano cardíaco Efeitos colaterais da irradiação fracionada Radiobiology Black grape juice Heart damage Secondary effect of whole brain irradiation CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Radiobiologia Suco de uva Dano cardíaco Efeitos colaterais da irradiação fracionada Radiobiology Black grape juice Heart damage Secondary effect of whole brain irradiation CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
The ionizing radiation exposure is able to affect the organic functions. The acute exposure produce several side effects as immunosuppression, gastrointestinal diseases, dermatitis and cardiac damage. Fractionated and localized exposure used for cancer therapy can be produced systemic side effects as anorexia and tissue necrosis. The present thesis shows two the results of two different models of radiobiology. The aim of the first study was to evaluate the radiomodifier effect in heart of black grape juice (BGJ) by animal model of acute radiation syndrome. Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source and two groups were sham-irradiated. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation. After euthanasia, the blood was collected for lactate dehydrogenase (LDH) quantification on serum and the hearts were excised and homogenized for lipid peroxidation measurement. High concentration of metabolites from lipid peroxidation in heart determined by reactive thiobarbituric acid reactive substances assay (TBARS), and high LDH level on serum were found only in gamma-irradiated group treated with placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD) analysis, which showed resveratrol (31.28 ± 0.04 mg/L) as the majority compound. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier. The second study investigated the secondary effects of fractionated whole brain irradiation (WBI). Radiotherapy is used for brain tumour treatment. WBI causes side effects such as neurocognitive impairments, anorexia and osteorradionecrosis. We used the BGJ as countermeasure to the side effects of WBI. Forty rats were exposed to 8 sessions of fractionated WBI. The total dose absorbed was 32 Gy. Forty rats were exposed to 8 sessions of fractionated WBI. The total dose absorbed was 32 Gy. The animals were divided into 4 groups equals to the studied groups in the first experiment. The rats received the BGJ or glucose and fructose solution 4 days before, during, and 4 days after WBI. Body weight, food and water consumption were measured during the experiment. The blood was collected 2 months after WBI and the mandibles were collected for morphometric and histological analysis. The irradiated and BGJ suplemented rats lost less weight than irradiated control rats (RG) in some days of WBI sessions, indicating a protective effect of BGJ. In some days, RJ rats ingested more food and water then RG rats. After WBI, all rats grew until day 61. Irradiated animals started losing weight again compared with controls as a consequence of mandibular osteoradionecrosis (ORN). Measurements performed on mandible showed that RG animals lost weight due to masticatory hypofunction. At microscopic level, osteoclastic activity and inflammation were apparent in mandibles of RG rats. Nevertheless, although BGJ did not completely restore the alterations induced by WBI, this antioxidant-rich beverage can be used to attenuate side effects of brain irradiation. In general, the BGJ offer protection to side effects induced by radiation in rats. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-12-17 2019-08-21T20:12:01Z 2019-08-21T20:12:01Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
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http://repositorio.ufsm.br/handle/1/17985 |
dc.identifier.dark.fl_str_mv |
ark:/26339/001300000w2z0 |
url |
http://repositorio.ufsm.br/handle/1/17985 |
identifier_str_mv |
ark:/26339/001300000w2z0 |
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por |
language |
por |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1815172405116534784 |