Oral Administration of Melatonin or Succinyl Melatonin Niosome Gel Benefits 5-FU-Induced Small Intestinal Mucositis Treatment in Mice.

Abstract

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.