Effects of trapidil on intestinal mucosal barrier function and bacterial translocation after intestinal ischemia and reperfusion in an experimental rat model

Abstract

Background: Intestinal ischemia and reperfusion may be the primary triggers of mucosal barrier impairment, cytokine expression, and bacterial translocation (BT). Trapidil is a phosphodiesterase and platelet-derived growth factor inhibitor that reduces lipid peroxidation and inhibits the production of cytokines. Objective: The goal of this study was to assess whether trapidil might protect the intestinal epithelial barrier by inhibiting lipid peroxidation and proinflammatory cytokines by testing the effect of trapidil on intestinal barrier function in an experimental ischemia/reperfusion (I/R) rat model. Methods: Trapidil was used in a rat model of intestinal barrier dysfunction caused by intestinal ischemia for 40 minutes followed by reperfusion for 12 hours. To do this, the rats were randomized to 1 of 4 treatment groups, as follows: (1) sham surgery and saline administration (1 mL IV) (Sham group); (2) sham surgery and trapidil administration (8 mg/kg IV) (Sham+T group); (3) I/R and saline administration (1 mL IV) (I/R group); and (4) I/R and trapidil administration (8 mg/kg IV) (I/R+T group). Intestinal barrier function was assessed by histopathologic examination, blood malondialdehyde (MDA) level, and BT. Results: The I/R+T group showed significantly less incidence of BT compared with the I/R group in the liver and reduced median colony count of translocated bacteria in mesenteric lymph nodes, liver, spleen, and peritoneum compared with the I/R group. Furthermore, the mean blood MDA level demonstrated that lipid peroxidation was significantly decreased in the I/R+T group compared with the I/R group. Histopathologic findings revealed that trapidil administration before reperfusion preserved intestinal mucosal integrity and inhibited the infiltration of inflammatory cells into the intestines. Conclusions: In this experimental study, a correlation seemed to exist between intestinal barrier dysfunction and BT. Intestinal barrier dysfunction may allow a large amount of bacteria to pass from the gut to distant organs. Trapidil treatment may inhibit BT by preserving intestinal barrier by inhibiting thromboxane A 2, lipid peroxidation, proinflammatory cytokines, and stimulated prostacyclin. Future dose- and time-dependent studies will be helpful in revealing the effects of trapidil on BT.