S-nitrosoglutathione accelerates recovery from 5-fluorouracil-induced oral mucositis.

Autor: Skeff MA; Laboratory of Cell Morphogenesis, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Brito GA; Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., de Oliveira MG; Institute of Chemistry, University of Campinas, UNICAMP, Campinas, SP, Brazil., Braga CM; Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Cavalcante MM; Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Baldim V; Institute of Chemistry, University of Campinas, UNICAMP, Campinas, SP, Brazil., Holanda-Afonso RC; Laboratory of Cell Morphogenesis, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Silva-Boghossian CM; Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Faculty of Dentistry, University of Grande Rio, Duque de Caxias, RJ, Brazil., Colombo AP; Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Ribeiro RA; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Moura-Neto V; Laboratory of Cell Morphogenesis, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, RJ, Brazil., Leitão RF; Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2014 Dec 05; Vol. 9 (12), pp. e113378. Date of Electronic Publication: 2014 Dec 05 (Print Publication: 2014).
DOI: 10.1371/journal.pone.0113378
Abstrakt: Introduction: Mucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side-effect of cancer therapy.
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.
Databáze: MEDLINE
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