Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / O tratamento de feridas cutÃneas crÃnicas resulta em altos custos e riscos de complicaÃÃes que podem atrasar a resoluÃÃo do processo de cicatrizaÃÃo. Neste estudo, uma formulaÃÃo farmacÃutica (pomada) foi desenvolvida contendo uma fraÃÃo proteica isolada do lÃtex de Himatanthus drasticus (HdLP) com o objetivo de investigar o seu efeito no processo de cicatrizaÃÃo de feridas excisionais em camundongos swiss machos (25Â3,0 g). Primeiramente, o teste de irritabilidade dermal em camundongos demonstrou que o tratamento tÃpico com a pomada contendo HdLP nÃo foi capaz de provocar reaÃÃes de irritaÃÃo na pele Ãntegra e na pele escarificada. A anÃlise macroscÃpica de feridas excisionais constatou que HdLP 0,5%, 1,0 % e 2,0% nÃo interferiu nos sinais flogÃsticos de edema e hiperemia, mas o tratamento com HdLP 2,0% acelerou a contraÃÃo das Ãlceras a partir do 9Â dia apÃs a induÃÃo cirÃrgica da lesÃo, antecipou o surgimento do tecido cicatricial e favoreceu a reepitelizaÃÃo completa das feridas. ApÃs a anÃlise macroscÃpica, a concentraÃÃo de HdLP 2,0% foi escolhida para o estudo histopatolÃgico (infiltrado leucocitÃrio, degranulaÃÃo de mastÃcitos, fibroplasia e colagÃnese) e de mediadores inflamatÃrios (mieloperoxidase (MPO), nÃveis de nitrito e citocinas prÃ- e anti-inflamatÃrias (TNF-α, IL-1β, IL-6 e IL-10). O tratamento com HdLP 2,0% foi capaz de diminuir o infiltrado polimorfonuclear e aumentar o mononuclear no 2Â dia mas nÃo interferiu no processo de degranulaÃÃo de mastÃcitos em nenhum perÃodo observado 2Â, 7Â e 9Â dias. Na fase inflamatÃria, HdLP 2,0% diminuiu a atividade de MPO, corroborando com a reduÃÃo da migraÃÃo de polimorfonucleares, e estimulou a liberaÃÃo de IL-1β e IL-10 no 2Â dia, alÃm disso, os nÃveis de nitrito foram reduzidos no 2Â e 4Â dias e elevados no 9Â dia. Durante a fase proliferativa, HdLP 2,0% estimulou a fibroplasia no 7Â e 9Â dias apÃs a cirurgia, o que possivelmente contribuiu para uma maior deposiÃÃo de colÃgeno observada no 9Â e 14Â dia. Conforme a anÃlise macroscÃpica previamente descrita, HdLP 2,0% favoreceu o processo de reepitelizaÃÃo das feridas excisionais mas nÃo interferiu na espessura do novo epitÃlio formado. Dessa forma, o conjunto dos resultados apresentados demonstram que o tratamento tÃpico com HdLP 2,0% modula a resposta inflamatÃria da cicatrizaÃÃo, influenciando nas etapas posteriores e acelerando a reparaÃÃo tecidual de feridas cutÃneas excisionais experimentais. / The treatment of chronic skin wounds results in high costs and risks of complications that could delay the resolution of the healing process. In this study, a pharmaceutical formulation (ointment) was developed containing an isolated protein fraction from Himatanthus drasticus latex (HdLP) in order to investigate its effect on the excisional wound healing in swiss mice (25Â3,0 g). Inicially, the dermal irritation test in mice demonstrated that topical treatment with the ointment containing HdLP was not able to cause reactions of irritation in intact skin and the damaged skinreactions. The macroscopic analysis showed that HdLP 0,5%, 1,0% and 2,0% did not affect the inflammatory signs of edema and hyperemia in excisional wounds but treatment with 2,0% HdLP accelerated contraction of ulcers from 9th day after surgical induction of injury, anticipated the appearance of scar tissue and favored a complete re-epithelialization of wounds.After macroscopic analysis, the concentration of HdLP 2,0% was chosen for the histopathological study (leukocyte infiltration, mast cell degranulation, fibroplasia and collagenesis) and inflammatory mediators (myeloperoxidase (MPO), levels of nitrite and pro- and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10). The treatment with HdLP 2,0% was able to decrease the polymorphonuclear infiltrate and increase the mononuclear on the 2nd day but had no effect on mast cell degranulation process in any period observed 2, 7 and 9 days. In the inflammatory phase, HdLP 2,0% decreased the MPO activity, confirming the reduction of migration of polymorphonuclear cells, and stimulated release of IL-1 β and IL-10 on day 2, moreover, the nitrite levels were reduced at 2 and 4 days and exalted on the 9th day. During the proliferative phase, HdLP 2,0% stimulated fibroplasia at 7 and 9 days after surgery, which probably contributed to increased collagen deposition observed in the 9th and 14th day. As the macroscopic analysis previously described, HdLP 2,0% favored the re-epithelialization process of excisional wounds but did not affect the thickness of newly formed epithelium. Therefore, all the results presented show that topical treatment with HdLP 2,0% modulates the inflammatory response of wound healing, influencing the subsequent phases and speeding up the tissue repair of experimental wounds excised.
| Identifer | oai:union.ndltd.org:IBICT/oai:www.teses.ufc.br:9288 |
| Date | 19 January 2015 |
| Creators | Tamiris de FÃtima Goebel de Souza |
| Contributors | Nylane Maria Nunes de Alencar, Danielle MacÃdo Gaspar, Raquel Sombra BasÃlio de Oliveira |
| Publisher | Universidade Federal do CearÃ, Programa de PÃs-GraduaÃÃo em Farmacologia, UFC, BR |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFC, instname:Universidade Federal do Ceará, instacron:UFC |
| Rights | info:eu-repo/semantics/openAccess |
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