Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal
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Data
2014-04-11
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Universidade Federal de Goiás
Resumo
Intestinal mucositis is a limiting factor in anticancer therapies by causing
gastrointestinal cell destruction reaching the majority of patients undergoing
chemotherapy/radiotherapy and is often responsible for treatment discontinuation.
Although several studies have already been conducted to treat this disease, there
are still no universally accepted and standardized protocols of treatment. Plant
species with anti-inflammatory and antioxidant properties have been considered for
the treatment of mucositis, among them Bidens pilosa L. (BP) (Asteraceae) and
Curcuma longa L. (CL) (Zingiberaceae). In this study, the effects of a formulation
containing plant extracts of Bidens pilosa L. (BP) and Curcuma longa L. (CL), both
with pharmaceutical technology of mucoadhesion in mice intestinal mucositis induced
by 5-fluoruoacil (5-FU) were studied. This formulation was administered orally
(gavage) for 6 days in each group of mice at doses of 75mg/kg + BP 3.75 mg / kg CL
100 mg / kg BP + 7.5 mg / kg or 125 mg CL / BP kg + 15 mg / kg CL. The treatment
with the formulations occurred during six days, and in parallel with mucositis
induction was performed with 5-FU (200 mg / kg, intraperitoneally) from day 4 to day
6. On day 7, the mice were euthanized and the duodenal portion of the intestine of
each animal was extracted to perform the histomorphometry technique. From this
analysis, the dose of 125 mg/kg mucoadhesive formulation showed best
effectiveness results and was then chosen for the realization of the other tests:
histopathology analysis, expression of Bax, Bcl-2, p53 and Ki-67 analysis via
immunohistochemistry technique; analysis of the activity of myeloperoxidase (MPO)
enzyme, and determination of malondialdehyde (MDA) levels. Furthermore, analysis
of weight change and hematologic parameters were performed. To prove safety of
the formulation, an oral toxicity test of mucoadhesive formulation, and effect
evaluation of the plant extracts on the animals’intestine not submitted to mucositis
were performed. The mucoadhesive formulation was able to assuage the
histopathological damage caused by 5-FU; reduced weight loss, reduced levels of
MPO and MDA; stimulated cell proliferation by increasing the expression of Ki-67;
besides decreasing apoptosis observed by analyzing the expression of Bax and Bcl-2. The formulation at a dose of 2000mg/kg showed no signs of toxicity. It can be
concluded that the formulation under study exerts preventive and/or therapeutic
effects to intestinal mucositis with potential to be used with associated to anticancer
treatment.
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BASTOS, Carla Caroline Cunha. Efeitos da formulação mucoadesiva de Bidens pilosa L. (Asteraceae) e Curcuma longa L. (Zingiberaceae) no tratamento da mucosite intestinal. 2014. 79 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2014.