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Type: Artigo de periódico
Title: S-nitrosoglutathione Accelerates Recovery From 5-fluorouracil-induced Oral Mucositis
Author: Skeff M.A.
Brito G.A.C.
De Oliveira M.G.
Braga C.M.
Cavalcante M.M.
Baldim V.
Holanda-Afonso R.C.
Silva-Boghossian C.M.
Colombo A.P.
Ribeiro R.A.
Moura-Neto V.
Leitao R.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.
Editor: Public Library of Science
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0113378
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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