Estudo dos efeitos do alfa-bisabolol na mucosite intestinal experimental induzida por 5-fluorouracil em camundongos

Abstract

Intestinal mucositis is one of the most debilitating side effects of 5-Fluorouracil treatment and is associated with pain, bacteremia and malnutrition. The destruction of the intestinal mucosa leads to reduced absorption of nutrients and greater vulnerability to infection. At present there is no effective treatment for this condition.Therefore, some therapeutic strategies have been tested with the aim

of improving the clinical picture of these patients.Research has shown that α- bisabolol, a monocyclic natural sesquiterpene alcohol found in the essential oils

of Chamomile (Matricaria chamomilla), Vanillosmopsis erythropappa and other plants has been shown to have antioxidant, anti-inflammatory, antinociceptive and cicatrizant activities.Thus, the objective of this work was to avaluate the effects of α-bisabolol on experimental intestinal mucositis induced by 5-FU. For this, male Swiss mice received 5-Fluorouracil (450 mg / kg, i.p. single dose). After induction of mucositis the animals received orogastric route for 3 days α-bisabolol at doses of 50, 100 and 200 mg / kg and the control group received DMSO 2%. Four hours after the last day of treatment the animals were sacrificed to remove the intestinal segments of jejunum and ileum for analysis of the following parameters: histological changes, morphometry, nitrite / nitrate levels, GSH, myeloperoxidase, immunohistochemistry for INOs and gastric emptying. Throughout the experiment the animals were weighed daily. The results that 5- FU induced impairment of the functional epithelial barrier with intestinal villi shortening, partial cryptic necrosis, cell vacuolization, presence of neutrophil infiltrate and GSH consumption. Animals treated with α-bisabolol showed improvement in intestinal architecture with recovery at villus height and decrease in crypt depth in segments of jejunum and ileum, decrease in neutrophil infiltrate, increase in GSH levels and significantly reversed mastocytosis and induced leukopenia By 5-FU, in addition to reducing nitrite levels. α -bisabolol at the dose of 100 mg / kg decreased iNOs expression and gastric retention time. In conclusion, our results evidence that the administration of α-bisabolol attenuated the inflammatory damage through the reduction of MPO and iNOs expression, besides reducing the oxidative stress with decrease of nitrite ions and increase of GSH. The compound further decreased the shortening of the villi and the depth of the crypts.