Efeito do β-Cariofileno em modelo de mucosite intestinal induzida por 5-fluorouracil: papel da via do óxido nítrico e da COX - 2

Abstract

Mucositis is a syndrome characterized by ulceration of the gastrointestinal mucosa and occurs in nearly 40% of cancer patients treated with 5-fluorouracil, but there is no specific therapeutic approach for this pathology. β-caryophyllene (BCF) is a sesquiterpene that has been extensively studied, since it demonstrates antioxidant and anti-inflammatory effects in several inflammatory conditions. Thus, the present study aims to investigate the effect of BCF on 5-FU-induced intestinal mucositis model. Male Swiss mice received saline (0.9%, i.p.) or 5-FU (450 mg / kg, i.p. single dose). After 24 hours of 5-FU administration, BCF (10, 30 or 100 mg/kg, gavage) was given on days 2 and 3, and the animals were euthanized on the fourth day of the experimental protocol. Segments of the small intestine were collected for analysis of the following parameters: weight loss, histological changes, leukogram, MDA, GSH, MPO, mast cell counts, and IL-1β and COX-2 labeling by immunohistochemistry. BCF did not prevent 5-FU induced weight loss, but at a dose of 10 mg/kg, it prevented leucopenia and reduced histopathological changes induced by chemotherapy in the duodenum. BCF also reduced (p<0.05) oxidative parameters (by decreasing MDA levels and increasing GSH) and inflammatory parameters (by reducing mast cell levels, MPO and IL-1β and COX-2 expression) induced by 5-FU. In the duodenum, administration of L-NAME or celecoxib did not reverse the effect of BCF, reducing histopathological changes induced by 5-FU. Therefore, the results indicate that BCF has protective, antioxidant and anti-inflammatory effects, without participation of the nitric oxide or COX-2 pathway, in the duodenum of the 5-FU induced intestinal mucositis model.