Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats.

Abstract

Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX. Wistar albino rats were randomly divided into three groups. Control (n = 8), (saline via oral gavage for 5days), MTX (n = 8), (60mg/kg single dose MTX intraperitoneally on the 1st day and for the following 4days saline via oral gavage), and MTX + chitosan (n = 8), (1st day single dose 60mg/kg MTX intraperitoneally and followed with 200mg/kg chitosan via oral gavage for 4days). After 24h of the last dose, the animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-β), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-β, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared those of the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + chitosan group, all the values were close to those of the control group. It was demonstrated that chitosan has a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.