Toxicidade aguda e efeito anti-inflamat?rio do extrato das folhas de Miconia ferruginata DC. em modelo experimental da Distrofia Muscular de Duchenne

Autor: Corr?a, Paula Mariana Munno Guimar?es
Přispěvatelé: Machado, Alex Sander Dias, Peixoto, Marco Fabr?cio Dias, Oliveira, Eduardo de Jesus, Machado, Thais Peixoto Gaiad, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM)
Jazyk: portugalština
Rok vydání: 2020
Předmět:
Zdroj: Repositório Institucional da UFVJM
Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM)
instacron:UFVJM
Popis: O presente trabalho foi realizado com apoio da Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - Brasil (CAPES) - C?digo de Financiamento 001. Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2021-04-22T19:32:33Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) paula_mariana_munno_guimaraes_correa.pdf: 5403017 bytes, checksum: 53fc47b39f2bf8a67abe60874bcfed82 (MD5) Approved for entry into archive by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2021-04-22T19:33:51Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) paula_mariana_munno_guimaraes_correa.pdf: 5403017 bytes, checksum: 53fc47b39f2bf8a67abe60874bcfed82 (MD5) Made available in DSpace on 2021-04-22T19:33:52Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) paula_mariana_munno_guimaraes_correa.pdf: 5403017 bytes, checksum: 53fc47b39f2bf8a67abe60874bcfed82 (MD5) Previous issue date: 2020 Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) A distrofia Muscular de Duchenne ? o tipo mais comum e mais grave das distrofias musculares, relacionada ? altera??o gen?tica e aus?ncia da prote?na distrofina, que promove um efeito progressivo e r?pido na degenera??o muscular. Os corticosteroides s?o os f?rmacos mais utilizados no tratamento dessa patologia, se mostrando eficientes na redu??o da sua progress?o, por?m s?o apontados v?rios efeitos adversos associados a essa terap?utica. Assim, terapias com menor toxicidade, especialmente derivadas de plantas medicinais, t?m sido testadas para promover melhora do quadro cl?nico e da qualidade de vida dos pacientes. Devido ao potencial antioxidante e anti-inflamat?rio da esp?cie Miconia ferruginata demostrado em testes in vitro, o objetivo desta pesquisa foi avaliar, in vivo, a toxicidade aguda e os efeitos anti-inflamat?rios do extrato aquoso das folhas de M. ferruginata, em modelo animal da distrofia de Duchenne. Para isso, os camundongos mdx foram tratados por via intraperitoneal com as doses de 50, 100, 200, 300 e 2000 mg/kg do extrato aquoso da planta, segundo protocolo de toxicidade aguda em dose ?nica, e mantidos em observa??o por 14 dias. Por meio do screning hipocr?tico e avalia??o de consumo de ?gua, alimento e peso corporal foram determinados fatores associados ? faixa de toxicidade do extrato e c?lculo da dose letal de 50% (DL50). Al?m disso, foram avaliados par?metros morfol?gicos (macro e microsc?picos), presen?a de infiltrado inflamat?rio, quantifica??o de fibrose e an?lises imuno-histoqu?micas para os tecidos do f?gado, pulm?o e m?sculo tibial anterior. Os resultados obtidos mostraram que para a dose de 2000 mg/kg houve elevada toxicidade com compromentimento respirat?rio, neurotoxicidade, altera??es histopatol?gicas e morfol?gicas consider?veis nos tecidos avaliados. Al?m disso, nesta dose houve letalidade de 100% no per?odo de at? 48 horas. J? para as outras doses avaliadas (300, 200, 100 e 50 mg/kg), os animais n?o apresentaram altera??es comportamentais e nem houve sinais de toxicidade. Com a administra??o do extrato aquoso houve uma redu??o dose-dependente das altera??es histopatol?gicas e morfol?gicas, bem como redu??o da fibrose, inflama??o tecidual, de marcadores de extresse celular (HSP70) e aumento de marcadores antiapopt?ticos (MCL-1). De forma geral, a dose de 50 mg/kg mostrou ter um elevado potencial regenerativo tecidual e anti-inflamat?rio, visto que nesta dose, para todos os tecidos avaliados, houve revers?o da fibrose e redu??o dr?stica da inflama??o local. Disserta??o (Mestrado) ? Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2020. Duchenne Muscular dystrophy is the most common and severe type of muscular dystrophy, related to genetic alteration and absence of dystrophin protein, which promotes a progressive and rapid effect on muscle degeneration. Corticosteroids are the most used drugs in the treatment of this pathology, proving to be efficient in reducing its progression, however several adverse effects associated with this therapy are pointed out. Thus, therapies with less toxicity, especially those derived from medicinal plants, have been tested to improve the clinical condition and quality of life of patients. Due to the antioxidant and anti-inflammatory potential of the Miconia ferruginata species demonstrated in vitro tests, the aim of this research was to evaluate, in vivo, the acute toxicity and anti-inflammatory effects of the aqueous extract of the leaves of M. ferruginata, in an animal model of Duchenne dystrophy. For this, the mdx mice were treated intraperitoneally with doses of 50, 100, 200, 300 and 2000 mg/kg of aqueous plant extract, according to a single dose acute toxicity protocol, and kept under observation for 14 days. Through hypocratic screning and assessment of water, food and body weight consumption, factors associated with the toxicity range of the extract and calculation of the 50% lethal dose (LD50) were determined. In addition, morphological parameters (macro and microscopic), presence of inflammatory infiltrate, fibrosis quantification and immunohistochemical analyzes for the tissues of the liver, lung and anterior tibial muscle were evaluated. The results obtained showed that for the 2000 mg/kg dose there was high toxicity with respiratory impairment, neurotoxicity, considerable histopathological and morphological changes in the evaluated tissues. In addition, in this dose there was 100% lethality in the period up to 48 hours. For the other doses evaluated (300, 200, 100 and 50 mg / kg), the animals showed no behavioral changes and there were no signs of toxicity. With the administration of the aqueous extract there was a dose-dependent reduction in histopathological and morphological changes, as well as a reduction in fibrosis, tissue inflammation, cell stress markers (HSP70) and an increase in anti-apoptotic markers (MCL-1). In general, the dose of 50 mg/kg showed a high tissue regenerative and anti-inflammatory potential, since in this dose, for all evaluated tissues, there was reversal of fibrosis and a drastic reduction of local inflammation.
Databáze: OpenAIRE
Externí odkaz: