Oral Administration of Melatonin or Succinyl Melatonin Niosome Gel Benefits 5-FU-Induced Small Intestinal Mucositis Treatment in Mice.
Administration, Oral
Animals
Fluorouracil
/ toxicity
Interleukin-1beta
/ metabolism
Intestinal Mucosa
/ drug effects
Intestine, Small
/ pathology
Lipid Peroxidation
/ drug effects
Liposomes
/ chemistry
Male
Melatonin
/ administration & dosage
Mice
Mice, Inbred ICR
Mucositis
/ chemically induced
Particle Size
Tumor Necrosis Factor-alpha
/ metabolism
5-fluorouracil
melatonin
niosome
small intestinal mucositis
succinyl melatonin
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
01 Jul 2021
01 Jul 2021
Historique:
received:
30
06
2020
accepted:
20
01
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
11
8
2021
Statut:
epublish
Résumé
Mucositis is one of the most adverse effects of 5-fluorouracil (5-FU) and had no standard drug for treatment. Melatonin is a neurohormone, and can ameliorate radiotherapy-induced small intestinal mucositis. Melatonin encapsulated in niosomes improved its poor bioavailability. Succinyl melatonin, a melatonin derivative, showed prolonged release compared with melatonin. This study investigated the efficacy of melatonin niosome gel (MNG) and succinyl melatonin niosome gel (SNG) in 5-FU-induced small intestinal mucositis treatment in mice. MNG and SNG with particle sizes of 293 and 270 nm were shown to have mucoadhesive potentials. The effect of a daily oral application of MNG, SNG, or fluocinolone acetonide gel (FAG, positive control) was compared to that of the normal group. The body weight, food consumption, histology, Fourier transform infrared (FTIR) spectroscopy, inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β), and malondialdehyde (MDA) in the small intestine were monitored. The results showed decreased %body weight and food consumption in all 5-FU-injected groups compared with the normal group. The MNG and SNG treatments maintained the food consumption and the normal integrity of the small intestines, as evidenced by villus length and crypt depth, similar to the observations in the normal groups. The FTIR spectra showed no change in lipids of the MNG and SNG groups compared with the normal group. Moreover, SNG could reduce IL-1β content to a level that was not different from the level in the normal groups. Therefore, the oral application of MNG and SNG could protect against 5-FU-induced small intestinal mucositis in mice.
Identifiants
pubmed: 34212283
doi: 10.1208/s12249-021-01941-y
pii: 10.1208/s12249-021-01941-y
doi:
Substances chimiques
Interleukin-1beta
0
Liposomes
0
Tumor Necrosis Factor-alpha
0
Melatonin
JL5DK93RCL
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
200Références
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