ABSTRACT
Oxidative stress, inflammation and apoptosis are the primary inducers of Methotrexate (MTX)-induced mucositis. This research aimed to determine whether apocynin (APO) could protect against MTX-induced mucositis. The antioxidants, anti-inflammatory and anti-apoptotic actions of APO in this model will be evaluated. The experiment was performed on 32 rats. A single dose (20 mg/kg) of MTX was injected i.p. to induce intestinal mucositis. APO was given orally once per day at a dose of 100mg/kg (five days prior to and five days following an MTX injection). APO safeguarded the histological structure of the duodenal mucosa, as observed by the conserved histology of goblet cells (villi and crypts). APO mitigated oxidative stress by reducing intestin MDA and raising GSH, SOD and GST, also suppressing NF-κB mRNA expression. Intestinal content of proinflammatory cytokines was reduced in APO-treated MTX rats, with downregulation of proinflammatory iNOS and upregulation of anti-inflammatory PPAR-γ proteins. The intestinal mucosa of rats treated with APO and MTX displayed weekly positive immune staining for cleaved caspase-3. APO upregulate the anti-apoptotic Bcl2 mRNA and down regulate the proapoptotic Bax and Puma mRNA in the duodenal mucosa. The results indicate the possibility of using APO as a novel therapeutic agent to prevent MTX-induced mucositis.
