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Type: Artigo
Title: S-nitrosoglutathione accelerates recovery from 5-fluorouracil-induced oral mucositis
Author: Skeff, Maria Adriana
Brito, Gerly A. C.
Oliveira, Marcelo G. de
Braga, Cintia M.
Cavalcante, Matheus M.
Baldim, Victor
Holanda-Afonso, Rosenilde C.
Silva-Boghossian, Carina M.
Colombo, Ana Paula
Ribeiro, Ronaldo A.
Moura-Neto, Vivaldo
Leitão, Renata F. C.
Abstract: Introduction: Mucositis induced by anti-neoplastic drugs is an important, doselimiting and costly side-effect of cancer therapy. Copyright: Aim: To evaluate the effect of the topical application of S-nitrosoglutathione (GSNO), a nitric oxide donor, on 5-fluorouracil (5-FU)-induced oral mucositis in hamsters. Materials and Methods: Oral mucositis was induced in male hamsters by two intraperitoneal administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) followed by mechanical trauma on the fourth day. Animals received saline, HPMC or HPMC/GSNO (0.1, 0.5 or 2.0 mM) 1 h prior to the 5-FU injection and twice a day for 10 or 14 days. Samples of cheek pouches were harvested for: histopathological analysis, TNF-α and IL-1β levels, immunohistochemical staining for iNOS, TNF-α, IL-1β, Ki67 and TGF-β RII and a TUNEL assay. The presence and levels of 39 bacterial taxa were analyzed using the Checkerboard DNA-DNA hybridization method. The profiles of NO released from the HPMC/GSNO formulations were characterized using chemiluminescence. Results: The HPMC/GSNO formulations were found to provide sustained release of NO for more than 4 h at concentration-dependent rates of 14 to 80 nmol/mL/h. Treatment with HPMC/GSNO (0.5 mM) significantly reduced mucosal damage, inflammatory alterations and cell death associated with 5-FU-induced oral mucositis on day 14 but not on day 10. HPMC/GSNO administration also reversed the inhibitory effect of 5-FU on cell proliferation on day 14. In addition, we observed that the chemotherapy significantly increased the levels and/or prevalence of several bacterial species. Conclusion: Topical HPMC/GSNO accelerates mucosal recovery, reduces inflammatory parameters, speeds up re-epithelization and decreases levels of periodontopathic species in mucosal ulcers
Subject: Mucosite
Country: Estados Unidos
Editor: Public Library of Science
Rights: Aberto
Identifier DOI: 10.1371/journal.pone.0113378
Date Issue: 2014
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