The effects of agmatine on intestinal ischemia reperfusion model in rats

Various studies have documented that the intestinal ischemia-reperfusion (I/R) results in alterations of the electrical activity and motility as well as the damage of mucosal and the structural integrity in gut. The purpose of the present study is to investigate the possible effects of agmatine on injury induced by intestinal I/R. Total of 32 adult male Wistar-Albino rats were randomly divided into four groups: 1) Sham-operated control; 2) I/R control; 3) Agmatine-treated sham control; and 4) Agmatine-treated I/R group. Intestinal ischemia was generated by the occlusion of the superior mesenteric artery (SMA) by a clamp for 30 minutes followed by the period of reperfusion lasting 3 hours. Intraperitoneal administration of agmatine at a dose of 10 mg/kg was carried out just prior to the beginning of the reperfusion period. Immediately after the end of the reperfusion phase, the tissues of terminal ileum were carefully isolated and collected followed by the evaluation of contractile responses to both carbachol and potassium chloride (KCl) in isolated-organ bath. Malondialdehyde (MDA) and reduced glutathione (GSH) contents as well as myeloperoxidase (MPO) activity levels of the ileal tissues were measured in addition to the histopathological evaluation of the tissues. The expression of the tissue inducible form of nitric oxide synthase (iNOS) was determined immunohistochemically. Additionally, plasma levels of such proinflammatory cytokines as TNF, IL-1 ?, IFN-?, MCP-1, GMCSF and IL-4 were measured by using the technique of flowcytomety. The contractile responses of the I/R group were significantly lower than those of the control group. The decreased contractile responses were improved remarkably by the treatment with agmatine. The content of MDA and the activity of MPO were both elevated significantly in tissues of the I/R group. Meaningful decrease in the GSH content and the advanced degree of the tissue damage were also evident in the same group. The treatment with agmatine appeared to be significantly effective in reducing the amounts of MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The I/R-induced increases in the expressions of iNOS, IL-1 ?, and IFN-? was brougt back to the sham control levels by the treatment with agmatine. In conclusion, the present study have shown that the treatment with agmatin exerted protective effects on the I/R-induced intestinal injury via regulation of the contractile responses, improvement of the biochemical parameters, attenuation of the histological damage, and modulation of the systemic inflammatory response. The beneficial effects that we have observed were possibly the results of the reduction of oxidative stress, decrease of the proinflammatory cytokines, and lowered expression of iNOS. Keywords: intestinal contractility; intestinal ischemia-reperfusion injury; agmatine.