S-Nitrosoglutathione Accelerates Recovery from 5-Fluorouracil-Induced Oral Mucositis

Author(s):Show less -

Skeff, Maria Adriana ^{[1, 2]} ; Brito, Gerly A. C. ^[2] ; de Oliveira, Marcelo G. ^[3] ; Braga, Cintia M. ^[2] ; Cavalcante, Matheus M. ^[2] ; Baldim, Victor ^[3] ; Holanda-Afonso, Rosenilde C. ^[1] ; Silva-Boghossian, Carina M. ^{[4, 5]} ; Colombo, Ana Paula ^[4] ; Ribeiro, Ronaldo A. ^[6] ; Moura-Neto, Vivaldo ^{[1, 7]} ; Leita, Renata F. C. ^[2]

Affiliation

^[1] Univ Fed Rio de Janeiro, Inst Biomed Sci, Lab Cell Morphogenesis, Rio De Janeiro, RJ - Brazil

^[2] Univ Fed Ceara, Sch Med, Dept Morphol, Fortaleza, Ceara - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Inst Chem, Campinas, SP - Brazil

^[4] Univ Fed Rio de Janeiro, Inst Microbiol, BR-21941 Rio De Janeiro, RJ - Brazil

^[5] Univ Grande Rio, Fac Dent, Duque De Caxias, RJ - Brazil

^[6] Univ Fed Ceara, Sch Med, Dept Physiol & Pharmacol, Fortaleza, Ceara - Brazil

^[7] Inst Estadual Cerebro Paulo Niemeyer, Rio De Janeiro, RJ - Brazil

• Document type: Journal article
• Source: PLoS One; v. 9, n. 12 DEC 5 2014.
• Web of Science Citations: 11

Abstract

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-alpha and IL-1 beta levels, immunohistochemical staining for iNOS, TNF-alpha, IL-1 beta, Ki67 and TGF-beta 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. (AU)

• FAPESP's process: 08/57560-0 - Effects of green tea (Camellia sinensis), cocoa and nitric oxide donor on diabetic nephropathy and retinopathy: contribution of the reduction of oxidative stress and inflammation and elevation of nitric oxide
• Grantee: Jose Butori Lopes de Faria
• Support Opportunities: Research Projects - Thematic Grants