The potential protective effect of modafinil in intestinal ischemic reperfusion-induced in rats

Abstract

ObjectiveIntestinal ischemia reperfusion (IR) is a pathophysiologic process that leads to oxidative stress and acute inflammatory responses. Understanding the mechanisms explaining this inflammation is essential to developing therapeutic strategies. Therefore, the purpose of this study was to evaluate the protective outcome of modafinil (Mod) against intestinal damages caused by intestinal IR injury. Methods/materialsFourty adult Male Wistar rats were randomly divided into four groups: sham control group; intestinal IR group; Mod pre-treated IR group and Mod post-treated IR group. Mod in a dose of 10 mg/kg was injected intraperitoneally once daily for 7 days pre or post IR treatment. ResultsMod significantly attenuated the IR induced elevations in intestinal malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin 1-β (IL-1β) and P-glycoprotein (P-gp) levels, caspase-3 activity. However, a significant increase in TAC was reported as compared with the IR group but its post-treated IR group was highly protective. Mod post-treatment down-regulated the IR induced cyclo-oxygenase-2 (COX-2) over-expression. Distorted mucosa with loss of surface epithelial cells, epithelial separation oedematous lamina propria and inflammatory cellular infiltration detected by histopathological examination of intestinal tissue, were markedly ameliorated by Mod post-treatment.On the other hand, Mod pre-treatment showed less protection against intestinal IR in rats. ConclusionCurrent study suggests that Mod post-treatment ameliorated intestinal damages, so it can be considered a potential therapeutic agent to protect against the major clinical challenge of intestinal injury resulting from IR.