Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMT |
Texto Completo: | http://ri.ufmt.br/handle/1/4841 |
Resumo: | Colon cancer is one of the most prevalent neoplasms globally, with high mortality rates. Therefore, there is a constant search for alternative treatment and prevention measures. Some scientific studies have shown a high anticarcinogenic potential in natural and synthetic chemical substances, such as botryosphaeran, a fungal exopolysaccharide produced by Botryosphaeria rhodina MAMB-05. Botryosphaeran has demonstrated anticarcinogenic effects through immunomodulatory, cytotoxic and antioxidant activities. However, no scientific studies have been found related to the antitumor effects of botryosphaeran on colon cancer, and there is a need to investigate its potential antiproliferative activities in experimental models of colon carcinogenesis. Thus, the present study aimed to evaluate the chemoprotective capacity of botryosphaeran on initiation of 1,2-dimethyldrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Animals were divided into three groups: positive control (PC), negative control (NC) and botryosphaeran test (BT). PC group received subcutaneous injections of DMH (4 x 40 mg/kg b.w.) twice a week; NC group received similar subcutaneous injections of EDTA solution (DMH vehicle); BT group received daily doses of botryosphaeran (30 mg/kg b.w.) via gavage for 4 weeks and subcutaneous injections of DMH (4 x 40 mg/kg b.w.) twice a week. On the 13th week, animals were euthanized by anesthetic deepening and colon, kidney and liver were collected. We evaluated the evolution of body weight, food and water intake, absolute and relative weight of liver and kidneys, development of aberrant crypt foci (ACFs) and mucindepleted foci (MDFs), and the rates of mitosis, apoptosis and inflammatory infiltrate in histological sections stained with hematoxylin-eosin (HE). Statistical analysis was performed using one-way variance analysis (ANOVA) followed by Tukey’s test. Differences were considered significant when p < 0.05. Botryosphaeran caused no changes in food and water intake and showed no toxicity. However, the animals showed a significant reduction in weight gain during the first 4 weeks of treatment, which may be related to different mechanisms of action of botryosphaeran on body weight control. Botryosphaeran significantly reduced the development of ACs, ACFs and MDFs, demonstrating an important antioxidant activity, and significantly reduced the rates of inflammatory infiltrate in the animals’ distal colon, evidencing their immunomodulatory activity. There were no significant differences in the rates of apoptosis and mitosis in the colon, and the method of analysis may have influenced these results. In conclusion, botryosphaeran demonstrated a potential chemopreventive activity on the development of colon cancer, standing out as a possible therapeutic agent. However, further investigations are necessary to explore its exact mechanisms of action. |
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Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machosCâncer de cólonBotriosferanaQuimioprevençãoCNPQ::CIENCIAS DA SAUDEColon cancerBotryosphaeranChemopreventionColon cancer is one of the most prevalent neoplasms globally, with high mortality rates. Therefore, there is a constant search for alternative treatment and prevention measures. Some scientific studies have shown a high anticarcinogenic potential in natural and synthetic chemical substances, such as botryosphaeran, a fungal exopolysaccharide produced by Botryosphaeria rhodina MAMB-05. Botryosphaeran has demonstrated anticarcinogenic effects through immunomodulatory, cytotoxic and antioxidant activities. However, no scientific studies have been found related to the antitumor effects of botryosphaeran on colon cancer, and there is a need to investigate its potential antiproliferative activities in experimental models of colon carcinogenesis. Thus, the present study aimed to evaluate the chemoprotective capacity of botryosphaeran on initiation of 1,2-dimethyldrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Animals were divided into three groups: positive control (PC), negative control (NC) and botryosphaeran test (BT). PC group received subcutaneous injections of DMH (4 x 40 mg/kg b.w.) twice a week; NC group received similar subcutaneous injections of EDTA solution (DMH vehicle); BT group received daily doses of botryosphaeran (30 mg/kg b.w.) via gavage for 4 weeks and subcutaneous injections of DMH (4 x 40 mg/kg b.w.) twice a week. On the 13th week, animals were euthanized by anesthetic deepening and colon, kidney and liver were collected. We evaluated the evolution of body weight, food and water intake, absolute and relative weight of liver and kidneys, development of aberrant crypt foci (ACFs) and mucindepleted foci (MDFs), and the rates of mitosis, apoptosis and inflammatory infiltrate in histological sections stained with hematoxylin-eosin (HE). Statistical analysis was performed using one-way variance analysis (ANOVA) followed by Tukey’s test. Differences were considered significant when p < 0.05. Botryosphaeran caused no changes in food and water intake and showed no toxicity. However, the animals showed a significant reduction in weight gain during the first 4 weeks of treatment, which may be related to different mechanisms of action of botryosphaeran on body weight control. Botryosphaeran significantly reduced the development of ACs, ACFs and MDFs, demonstrating an important antioxidant activity, and significantly reduced the rates of inflammatory infiltrate in the animals’ distal colon, evidencing their immunomodulatory activity. There were no significant differences in the rates of apoptosis and mitosis in the colon, and the method of analysis may have influenced these results. In conclusion, botryosphaeran demonstrated a potential chemopreventive activity on the development of colon cancer, standing out as a possible therapeutic agent. However, further investigations are necessary to explore its exact mechanisms of action.O câncer de cólon é uma das neoplasias mais incidentes a nível global, apresentando altas taxas de mortalidade. Portanto, há uma busca constante por medidas alternativas de tratamento e prevenção. Alguns trabalhos científicos têm demonstrado o alto potencial anticarcinogênico de substâncias químicas naturais e sintéticas, como a botriosferana, um exopolissacarídeo produzido pelo fungo Botryosphaeria rhodina MAMB-05. A botriosferana tem demonstrado uma importante atividade antitumoral por meio de efeitos antioxidantes, citotóxicos e imunomoduladores. No entanto, até o momento, não foram encontrados trabalhos científicos relacionados à atividade anticarcinogênica da botriosferana sobre o câncer de cólon, havendo a necessidade de se investigar seus potenciais efeitos quimiopreventivos em modelos experimentais de carcinogênese química. Assim, o presente trabalho teve como objetivo avaliar a capacidade quimioprotetora da botriosferana sobre a etapa de iniciação da carcinogênese experimental de cólon induzida pela administração de 1,2-dimetilhidrazina (DMH) em ratos Wistar machos. Os animais foram divididos em três grupos experimentais: controle positivo (CP); controle negativo (CN) e teste botriosferana (BT). O grupo CP recebeu aplicações subcutâneas de quatro doses de 40 mg/kg de DMH duas vezes por semana; o grupo CN recebeu aplicações subcutâneas similares de 0,37 mg/kg de EDTA; e o grupo BT recebeu doses diárias de botriosferana (30 mg/kg, via gavagem, durante 4 semanas) e quatro doses de 40 mg/kg de DMH. Na 13ª semana os animais foram eutanasiados por aprofundamento em anestesia e realizou-se a coleta dos cólons, rins e fígado. Avaliou-se a evolução do peso corpóreo, o consumo de água e ração, o peso absoluto e relativo dos rins e fígado, o desenvolvimento de focos de criptas aberrantes (FCAs) e focos depletados de mucina (FDMs) e os índices de mitose, apoptose e filtrado inflamatório em cortes histológicos corados com hematoxilina-eosina (HE). A análise estatística foi realizada por meio da análise de variância one-way (ANOVA) seguida pelo Teste de Tukey, sendo as diferenças consideradas significativas quando p < 0,05. A botriosferana não alterou o consumo de água e ração e nem apresentou toxicidade hepática ou renal. No entanto, os animais apresentaram uma significativa redução no ganho de peso durante as primeiras quatro semanas do experimento, que pode estar relacionada a diferentes mecanismos de atuação da botriosferana sobre o controle do peso corpóreo. A botriosferana reduziu significativamente o desenvolvimento de FCAs e FDMs, demonstrando uma importante atividade antioxidante, e reduziu significativamente as taxas de infiltrado inflamatório no cólon distal dos animais, evidenciando sua atividade imunomodulatória. Não foram observadas diferenças significativas nos índices de apoptose e mitose, acredita-se que a técnica utilizada possa ter influenciado nesses resultados. Por fim, concluímos que a botriosferana apresentou um potencial efeito quimiopreventivo sobre o desenvolvimento do câncer de cólon, se destacando como um possível agente terapêutico. Entretanto, seus exatos mecanismos de ação precisam ser melhor investigados por meio de análises mais detalhadas.Universidade Federal de Mato GrossoBrasilInstituto de Ciências da Saúde (ICS) - SinopUFMT CUS - SinopPrograma de Pós-Graduação em Ciências em SaúdeDias, Marcos Correahttp://lattes.cnpq.br/6197853669797333Dias, Marcos Correa303.669.798-50http://lattes.cnpq.br/6197853669797333Queiroz, Eveline Aparecida Isquierdo Fonseca de042.780.249-08http://lattes.cnpq.br/6880858782538903303.669.798-50Zapaterini, Joyce Regina305.632.208-13http://lattes.cnpq.br/6319835472797434Barbosa, Francielly Fernanda2023-11-21T15:45:57Z2021-08-262023-11-21T15:45:57Z2021-05-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisBARBOSA, Francielly Fernanda. Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos. 2021. 68 f. Dissertação (Mestrado em Ciências em Saúde) - Universidade Federal de Mato Grosso, Campus Universitário de Sinop, Instituto de Ciências da Saúde, Sinop, 2021.http://ri.ufmt.br/handle/1/4841porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMTinstname:Universidade Federal de Mato Grosso (UFMT)instacron:UFMT2023-11-23T06:01:35Zoai:localhost:1/4841Repositório InstitucionalPUBhttp://ri.ufmt.br/oai/requestjordanbiblio@gmail.comopendoar:2023-11-23T06:01:35Repositório Institucional da UFMT - Universidade Federal de Mato Grosso (UFMT)false |
dc.title.none.fl_str_mv |
Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos |
title |
Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos |
spellingShingle |
Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos Barbosa, Francielly Fernanda Câncer de cólon Botriosferana Quimioprevenção CNPQ::CIENCIAS DA SAUDE Colon cancer Botryosphaeran Chemoprevention |
title_short |
Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos |
title_full |
Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos |
title_fullStr |
Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos |
title_full_unstemmed |
Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos |
title_sort |
Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos |
author |
Barbosa, Francielly Fernanda |
author_facet |
Barbosa, Francielly Fernanda |
author_role |
author |
dc.contributor.none.fl_str_mv |
Dias, Marcos Correa http://lattes.cnpq.br/6197853669797333 Dias, Marcos Correa 303.669.798-50 http://lattes.cnpq.br/6197853669797333 Queiroz, Eveline Aparecida Isquierdo Fonseca de 042.780.249-08 http://lattes.cnpq.br/6880858782538903 303.669.798-50 Zapaterini, Joyce Regina 305.632.208-13 http://lattes.cnpq.br/6319835472797434 |
dc.contributor.author.fl_str_mv |
Barbosa, Francielly Fernanda |
dc.subject.por.fl_str_mv |
Câncer de cólon Botriosferana Quimioprevenção CNPQ::CIENCIAS DA SAUDE Colon cancer Botryosphaeran Chemoprevention |
topic |
Câncer de cólon Botriosferana Quimioprevenção CNPQ::CIENCIAS DA SAUDE Colon cancer Botryosphaeran Chemoprevention |
description |
Colon cancer is one of the most prevalent neoplasms globally, with high mortality rates. Therefore, there is a constant search for alternative treatment and prevention measures. Some scientific studies have shown a high anticarcinogenic potential in natural and synthetic chemical substances, such as botryosphaeran, a fungal exopolysaccharide produced by Botryosphaeria rhodina MAMB-05. Botryosphaeran has demonstrated anticarcinogenic effects through immunomodulatory, cytotoxic and antioxidant activities. However, no scientific studies have been found related to the antitumor effects of botryosphaeran on colon cancer, and there is a need to investigate its potential antiproliferative activities in experimental models of colon carcinogenesis. Thus, the present study aimed to evaluate the chemoprotective capacity of botryosphaeran on initiation of 1,2-dimethyldrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Animals were divided into three groups: positive control (PC), negative control (NC) and botryosphaeran test (BT). PC group received subcutaneous injections of DMH (4 x 40 mg/kg b.w.) twice a week; NC group received similar subcutaneous injections of EDTA solution (DMH vehicle); BT group received daily doses of botryosphaeran (30 mg/kg b.w.) via gavage for 4 weeks and subcutaneous injections of DMH (4 x 40 mg/kg b.w.) twice a week. On the 13th week, animals were euthanized by anesthetic deepening and colon, kidney and liver were collected. We evaluated the evolution of body weight, food and water intake, absolute and relative weight of liver and kidneys, development of aberrant crypt foci (ACFs) and mucindepleted foci (MDFs), and the rates of mitosis, apoptosis and inflammatory infiltrate in histological sections stained with hematoxylin-eosin (HE). Statistical analysis was performed using one-way variance analysis (ANOVA) followed by Tukey’s test. Differences were considered significant when p < 0.05. Botryosphaeran caused no changes in food and water intake and showed no toxicity. However, the animals showed a significant reduction in weight gain during the first 4 weeks of treatment, which may be related to different mechanisms of action of botryosphaeran on body weight control. Botryosphaeran significantly reduced the development of ACs, ACFs and MDFs, demonstrating an important antioxidant activity, and significantly reduced the rates of inflammatory infiltrate in the animals’ distal colon, evidencing their immunomodulatory activity. There were no significant differences in the rates of apoptosis and mitosis in the colon, and the method of analysis may have influenced these results. In conclusion, botryosphaeran demonstrated a potential chemopreventive activity on the development of colon cancer, standing out as a possible therapeutic agent. However, further investigations are necessary to explore its exact mechanisms of action. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-26 2021-05-31 2023-11-21T15:45:57Z 2023-11-21T15:45:57Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
BARBOSA, Francielly Fernanda. Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos. 2021. 68 f. Dissertação (Mestrado em Ciências em Saúde) - Universidade Federal de Mato Grosso, Campus Universitário de Sinop, Instituto de Ciências da Saúde, Sinop, 2021. http://ri.ufmt.br/handle/1/4841 |
identifier_str_mv |
BARBOSA, Francielly Fernanda. Efeitos da Botriosferana sobre a carcinogênese experimental de cólon em ratos Wistar machos. 2021. 68 f. Dissertação (Mestrado em Ciências em Saúde) - Universidade Federal de Mato Grosso, Campus Universitário de Sinop, Instituto de Ciências da Saúde, Sinop, 2021. |
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http://ri.ufmt.br/handle/1/4841 |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Universidade Federal de Mato Grosso Brasil Instituto de Ciências da Saúde (ICS) - Sinop UFMT CUS - Sinop Programa de Pós-Graduação em Ciências em Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Mato Grosso Brasil Instituto de Ciências da Saúde (ICS) - Sinop UFMT CUS - Sinop Programa de Pós-Graduação em Ciências em Saúde |
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Repositório Institucional da UFMT - Universidade Federal de Mato Grosso (UFMT) |
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jordanbiblio@gmail.com |
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