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Previous issue date: 2017-07-21 / A Mucosite Oral (MO) ? uma das principais complica??es envolvidas no tratamento do c?ncer, em
especial, da regi?o de cabe?a e pesco?o. Trata-se de uma inflama??o que afeta a mucosa da
cavidade oral e se caracteriza clinicamente pelo surgimento de les?es eritematosas, ulceradas e
dolorosas, o que pode ocasionar, em casos mais graves, interrup??o do tratamento quimioter?pico.
O objetivo deste estudo foi avaliar o efeito da Olmesartana (Olme), um antagonista do receptor AT1
da angiotensina II (Ang II), na mucosite oral. Foi realizado um ensaio pr?-cl?nico, in vivo,
randomizado, cego, com utiliza??o de grupos controles. 42 hamsters Golden Siriam foram divididos
em 6 grupos: Controle, Trauma Mec?nico, 5-FU, Olme 1mg/kg, Olme 5mg/kg e Olme 10mg/kg. Nos
grupos doentes a MO foi induzida nos dois primeiros dias do experimento com um quimioter?pico,
o 5-fluorouracil (5-FU, 60 mg/kg dia 1 e 40 mg/kg dia 2). Os animais foram pr?-tratados com Olme
oral (1, 5, ou 10 mg/kg) ou ve?culo (controles) 30 min antes da inje??o de 5-FU e diariamente at? o
d?cimo dia. As amostras de mucosa da bochecha foram submetidas a an?lise macrosc?pica,
histopatol?gica, an?lise de atividade enzim?tica bioqu?mica e imunohistoqu?mica. Rea??es em
cadeia de polimerase de transcriptase reversa (RT-PCRs) foram utilizadas para quantificar a
express?o de NF-?B, p65, PI3K e MKP1. Os n?veis de ?xido n?trico sintase induz?vel (iNOS) e
quinase regulada extracelularmente (ERK) foram analisados com Western Blot. O tratamento com
10 mg/kg de Olme reduziu os n?veis de ulcera??o, mieloperoxidase (MPO) e malonalde?do (MDA),
inflama??o celular, edema e hemorragia (todos p <0,05). O tratamento com Olme de 10 mg/kg
tamb?m reduziu os n?veis do fator de necrose tumoral (TNF)-?, interleucina (IL)-1?, aumentando a
express?o PI3K e diminuindo a express?o de NFKB, p65, MKP1 e diminuindo os n?veis de iNOS e
ERK1/2. A utiliza??o da Olme na dose de 10 mg/kg reduziu o dano e a inflama??o da mucosa
associados com a MO induzido por 5-FU. / Oral Mucositis (MO) is one of the main complications involved in the treatment of cancer,
especially in the head and neck region. It is an inflammation that affects the mucosa of the
oral cavity is clinically characterized by erythematous, ulcerated and painful lesions, Which
can lead, in more severe cases, to an interruption of chemotherapy treatment. The aim of
this study was to evaluate the effect of Olmesartan (Olme), an angiotensin II (Ang II) receptor
antagonist, on oral mucositis. A pre-clinical trial was performed, in vivo, randomized, blind,
with use of control groups. 42 Golden Siriam hamsters were divided into 6 groups: Control,
Mechanical Trauma, 5-FU, Olme 1mg/kg, Olme 5mg/kg and Olme 10mg/kg. In the diseased
groups MO was induced on the first two days of the experiment with a chemotherapeutic, 5-
fluorouracil (5-FU, 60 mg / kg day 1 and 40 mg / kg day 2). Animals were pretreated with
oral Olme (1, 5, or 10 mg/kg) or vehicle (control) 30 min before 5-FU injection and daily until
day 10. Cheek pouch samples were subjected to histopathologic analysis,
protein/immunology analysis, and immunoistochemistry. Reverse transcriptase polymerase
chain reactions (RT-PCRs) were used to quantitate expression of NF- ?Bp65, PI3K, and
MKP1. Inducible nitric oxide synthase (iNOS) and extracellular regulated kinase (ERK)1/2
levels were analysed with immunoblots. Treatment with 10 mg/kg Olme reduced ulceration,
myeloperoxidase (MPO) and malonaldehyde (MDA) levels, cellular inflammation, edema,
and hemorrhage (p<0.05). The 10 mg/kg Olme treatment also reduced tumour necrosis
factor (TNF)-?, interleukin (IL)-1?, increasing expression PI3K, and decreasing expression
of NFKBp65, MKP1, and decreasing iNOS and ERK1/2 levels. Olme at a dose of 10 mg/kg
prevented the mucosal damage and inflammation associated with 5-FU? induced OM.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/24093 |
| Date | 21 July 2017 |
| Creators | Ara?jo, Lorena de Souza |
| Contributors | 83806059420, Leit?o, Renata Ferreira de Carvalho, 43088139304, Lins, Ruthineia Di?genes Alves Uchoa, 87808838420, Ara?jo, Aurigena Antunes de |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM SA?DE COLETIVA, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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