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ALFABISABOLOL REVERSES THE MORPHOLOGICAL CHANGES INDUCED BY 5‐FU IN A MODEL OF INTESTINAL MUCOSITIS
Author(s) -
Cerqueira Gilberto Santos,
Godoy José Roberto Pimenta,
Lopes José,
Sobrinho Osvaldo Pereira Costa,
Medeiros Jand Venes Rolim,
Martins Conceição Silva,
Silva Costa Deiziane Viana
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.898.7
Subject(s) - mucositis , ileum , medicine , mast cell , gastroenterology , pharmacology , toxicity , immunology
5‐Fluorouracil (5‐FU) is broadly used to treatment of breast and colorectal cancer. However, it induces side effects as intestinal mucositis. Studies several has been performed to reduce the 5‐FU‐induced intestinal injury. In this regard, the α‐bisabolol (1‐methyl‐4‐(1,5‐dimethyl‐1‐hydroxhex‐4 (5)‐enyl)‐cyclohexen‐1) (BISA) has not yet been investigated in treatment of the 5‐FU‐induced intestinal mucositis. BISA is a monocyclic sesquiterpene found in essential oils of a variety of plants such as chamomile (Matricaria chamomilla, Compositae, syn. M. recutita), arnica (Arnica amplexicaulis and A. chamissonis), sage (Salvia stenophylla) incanus Eremanthus, Vanillosmopsis arborea among others. The aim of this study was to investigate the effect of BISA in the 5‐FU‐induced intestinal mucositis. Methods and Results Swiss Mice (weighing 25 to 30 grams) received DMSO 2% (control) or 5‐FU (450 mg/kg, i.p., single dose). After 24h, BISA (50, 100 or 200 mg/kg, dissolved at DMSO 2%) was injected by orogastric gavage during three days and the animals were euthanized four hours after last dose of BISA. The mice's body weight were evaluated daily. The ileum segments were collected to evaluate following parameters: histopatological analysis, count number of mast cells, reduced glutathione (GSH) and myeloperoxidase (MPO) levels. The ileum segments were extracted, measured and processed by histology routine and dyed with Hematoxiline eosine, Masson' Trichrome with toluidine blue 1% for mast cell counting and with picrosirius red for the total collagen fibers. 5‐FU promoted accentuated weight loss, shortening villus, loss of crypt architecture, intense inflammatory cells infiltrate along ileum layer. Moreover, 5‐FU increased the number of mast cells (53,80±3.426); DMSO (22,20±2.21); BISA‐50 (53,80±3.426);BISA‐100 (31,60±1.621); BISA‐200(79,20±4.923) and MPO levels (6,532±1,354);DMSO (2,402±0,2190);BISA 50 (4,678±0,3424);BISA 100(3,382±0,3239); BISA 200 (4,330±0,6093) in ileum, as well as decreased GSH levels compared with control group. The experimental group presented increased vascular density compared to the control group. Conclusion These results show that BISA had a protective effect against intestinal injury induced by 5‐FU. Moreover, we also showed that BISA reduces 5‐FU‐induced the mastocytosis. However, more tests are needed to evaluate the BISA mechanism in the 5‐FU‐induced intestinal mucositis. Support or Funding Information Footnotes: This study received funding of CAPES.