Abstract
Background: Oral mucositis, one of the most common complications of 5-Fluorouracil (5-FU) treatment, leads to several problems, including pain, diarrhea and malnutrition, and reduces the quality of life and subsequent treatments. Melatonin, a neurohormone with anti-inflammatory and antioxidant activities, was encapsulated in niosomes and embedded in a mucoadhesive gel formulation as a Melatonin Niosome Gel (MNG) to perform oral mucositis treatment.
Objective: This study aimed to investigate the effectiveness of MNG for the treatment of 5-FU-induced oral mucositis in mice.
Methods: Oral mucositis was induced in ICR mice by 5-FU and randomly assigned to receive daily applications of the topical oral MNG, a fluocinolone acetonide gel, a blank niosome gel, or no treatment for 5 days in comparison with a normal group. Average body weights, food consumption, and behaviors of the mice as well as microscopic histopathology, Fourier-Transform Infrared Spectroscopy (FTIR) analysis, proinflammatory cytokine levels, and oxidative stress markers of the tongues were monitored and collected after sacrifice.
Results: In comparison to the normal group, the average body weights of the 5-FU-MNG mice did not deviate from that of the normal group, nor was there a significant difference in the time to sleep or licking (p>0.05 for both parameters). In addition, the mice treated with MNG and fluocinolone acetonide did not show significantly different histopathological, FTIR, interleukin-1β or malondialdehyde (MDA) results in the tongues used as the oral tissue samples.
Conclusion: Topical MNG potentially inhibits inflammation and lipid oxidative stress in 5-FU-induced oral mucositis.
Keywords: Niosomes, melatonin, 5-fluorouracil, mucositis, anti-inflammation, antioxidant, Malondialdehyde (MDA).
[http://dx.doi.org/10.1038/nrc1074] [PMID: 12724731]
[http://dx.doi.org/10.1093/annonc/mdp165] [PMID: 19454447]
[http://dx.doi.org/10.1016/j.cden.2007.10.002] [PMID: 18154865]
[http://dx.doi.org/10.1002/cncr.20162] [PMID: 15108222]
[http://dx.doi.org/10.1038/onc.2015.398] [PMID: 26522725]
[http://dx.doi.org/10.1111/j.1601-0825.2010.01681.x] [PMID: 20846150]
[http://dx.doi.org/10.1038/s41385-019-0132-x] [PMID: 30647411]
[http://dx.doi.org/10.1111/jpi.12191] [PMID: 25388914]
[http://dx.doi.org/10.1038/ijos.2013.93] [PMID: 24357856]
[http://dx.doi.org/10.1056/NEJMoa040125] [PMID: 15602019]
[http://dx.doi.org/10.1002/1097-0142(20010815)92:4<875::AID-CNCR1396>3.0.CO;2-1] [PMID: 11550161]
[http://dx.doi.org/10.1016/j.jpainsymman.2013.07.014] [PMID: 24210702]
[http://dx.doi.org/10.1016/j.neuchi.2015.03.002] [PMID: 25908646]
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb05402.x] [PMID: 11268363]
[http://dx.doi.org/10.1016/j.bcp.2010.07.041] [PMID: 20696138]
[http://dx.doi.org/10.1016/S1043-6618(02)00089-0] [PMID: 12220952]
[http://dx.doi.org/10.1016/j.actatropica.2014.12.007] [PMID: 25542296]
[http://dx.doi.org/10.1371/journal.pone.0174474] [PMID: 28403142]
[http://dx.doi.org/10.1038/s41419-019-1556-7] [PMID: 30962427]
[http://dx.doi.org/10.1007/s10787-017-0332-5] [PMID: 28255737]
[http://dx.doi.org/10.1007/s12551-017-0256-8] [PMID: 28510090]
[http://dx.doi.org/10.1007/s12094-018-1934-0] [PMID: 30136132]
[http://dx.doi.org/10.1007/s00228-015-1873-4] [PMID: 26008214]
[http://dx.doi.org/10.1021/js970011z] [PMID: 9344167]
[http://dx.doi.org/10.4155/tde-2018-0001] [PMID: 29681235]
[PMID: 26514093]
[http://dx.doi.org/10.4155/tde-2017-0005] [PMID: 28530143]
[http://dx.doi.org/10.1089/acm.2017.0081] [PMID: 28657801]
[http://dx.doi.org/10.1371/journal.pone.0138746] [PMID: 26406888]
[http://dx.doi.org/10.1248/bpb.b14-00400] [PMID: 25747976]
[http://dx.doi.org/10.1371/journal.pone.0116213] [PMID: 25565296]
[http://dx.doi.org/10.1371/journal.pone.0135102] [PMID: 26266941]
[http://dx.doi.org/10.1016/j.tranon.2017.05.001] [PMID: 28666190]
[http://dx.doi.org/10.1016/B978-0-12-608606-5.50013-2]
[PMID: 14964052]
[http://dx.doi.org/10.1046/j.1365-2036.2003.01784.x] [PMID: 14616150]
[http://dx.doi.org/10.1016/S1773-2247(14)50025-1]
[http://dx.doi.org/10.1111/bcpt.12793] [PMID: 28374966]
[http://dx.doi.org/10.4028/www.scientific.net/AMR.902.70]
[http://dx.doi.org/10.1039/C5FD00184F] [PMID: 27048927]
[http://dx.doi.org/10.1038/nprot.2014.110] [PMID: 24992094]
[http://dx.doi.org/10.1080/01635589509514375] [PMID: 7644388]
[http://dx.doi.org/10.1634/stemcells.2008-0611] [PMID: 19038788]
[http://dx.doi.org/10.1007/BF02899559] [PMID: 1685035]
[http://dx.doi.org/10.1134/S106377451306014X]
[http://dx.doi.org/10.1007/BF00496860] [PMID: 823582]
[http://dx.doi.org/10.1038/nrn2606] [PMID: 19259101]
[http://dx.doi.org/10.1177/0022034514540174] [PMID: 24943201]
[http://dx.doi.org/10.1016/0009-9236(95)90040-3] [PMID: 7768078]
[http://dx.doi.org/10.1016/j.bcp.2008.01.011] [PMID: 18329632]
[http://dx.doi.org/10.4306/pi.2011.8.1.71] [PMID: 21519541]
[http://dx.doi.org/10.1593/neo.04169] [PMID: 15548350]
[http://dx.doi.org/10.1016/j.tranon.2018.03.014] [PMID: 29698934]
[http://dx.doi.org/10.1007/s00066-017-1119-8] [PMID: 28258409]
[http://dx.doi.org/10.15430/JCP.2013.18.4.322] [PMID: 25337561]
[http://dx.doi.org/10.1002/mnfr.201200082] [PMID: 22782912]
[http://dx.doi.org/10.3390/ijms18020279] [PMID: 28134832]