RESUMO
BACKGROUND: The irinotecan (CPT-11) causes intestinal mucositis and diarrhea that may be related to changes in the enteric nervous system (ENS). In inflammatory condition, mast cells release a variety of pro-inflammatory mediators that can interact with the ENS cells. It has not been explored whether CPT-11 is able to alter the enteric glial and neuronal cell, and the role of mast cells in this effect. Therefore, this study was conducted to investigate the effect of CPT-11 on the enteric glial and neuronal cells, as well as to study the role of mast cells in the CPT-11-induced intestinal mucositis. METHODS: Intestinal mucositis was induced in Swiss mice by the injection of CPT-11 (60 mg/kg, i.p.) once a day for 4 days following by euthanasia on the fifth day. To investigate the role of mast cells, the mice were pretreated with compound 48/80 for 4 days (first day, 0.6 mg/kg; second day, 1.0 mg/kg; third day, 1.2 mg/kg; fourth day, 2.4 mg/kg) to induce mast cell degranulation before the CPT-11 treatment. RESULTS: Here, we show that CPT-11 increased glial fibrillary acidic protein (GFAP) and S100ß gene and S100ß protein expressions and decreased HuC/D protein expression in the small intestine segments. Concomitantly, CPT-11 enhanced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and inducible nitric oxide synthase (iNOS) gene expression, associated with an increase in the total number macrophages (positive cells for ionized calcium-binding adapter molecule, Iba-1) and degranulated mast cells in the small intestine segments and caused significant weight loss. The pretreatment with compound 48/80, an inductor of mast cells degranulation, significantly prevented these CPT-11-induced effects. CONCLUSIONS: Our data suggests the participation of mast cells on the CPT-11-induced intestinal mucositis, macrophages activation, enteric reactive gliosis, and neuron loss.
Assuntos
Camptotecina/análogos & derivados , Sistema Nervoso Entérico/metabolismo , Gliose/induzido quimicamente , Gliose/metabolismo , Mastócitos/metabolismo , Neurônios/metabolismo , Animais , Antineoplásicos Fitogênicos/toxicidade , Camptotecina/toxicidade , Contagem de Células , Sistema Nervoso Entérico/efeitos dos fármacos , Sistema Nervoso Entérico/patologia , Gliose/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Irinotecano , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Distribuição AleatóriaRESUMO
OBJECTIVE: The aim of this study was to evaluate the morphological and morphometric alterations produced by raloxifene in the mammary epithelium of female rats in persistent estrus. MATERIALS AND METHODS: Twenty-one female Wistar-Hannover rats in persistent estrus induced by 1.25 mg of testosterone propionate were randomly divided into two groups: Group I (n = 10), receiving only water and used as control; Group II (experimental, n = 11), treated with 3 mg of raloxifene daily for 21 days. The first abdominoinguinal pair of mammary glands was extirpated and processed for morphological and morphometric evaluation. The data were statistically analysed using Student's t-test (p < 0.05). RESULTS: Morphology revealed signs of epithelial atrophy, and morphometry showed a significant reduction in the mean number of ducts and alveoli in the experimental group (12.82 +/- 0.42 and 2.91 +/- 0.53, respectively) when compared with the control group (28.70 +/- 1.15 and 7.20 +/- 0.57, respectively). This difference was statistically significant, both for the ducts and for the alveoli (p < 0.001). CONCLUSION: The present results indicate that, at the dose and during the time of treatment used, raloxifene induced atrophy of the mammary epithelium of rats in persistent estrus.