Bupropion reduces the inflammatory response and intestinal injury due to ischemia-reperfusion.

Intestinal ischemia-reperfusion (I/R) causes severe organ failure and intense inflammatory responses, which are mediated in part by the cytokine tumor necrosis factor-alpha (TNF-alpha). Bupropion is an antidepressant known to inhibit TNF-alpha production. We sought to examine the protective effects of bupropion on intestinal I/R injury in 15 male Sprague-Dawley rats that were randomized to sham surgery, 45 minutes of intestinal ischemia followed by 180 minutes reperfusion, or bupropion (100 mg/kg) before the intestinal I/R injury. To evaluate the systemic inflammatory response induced by intestinal I/R, we measured serum levels of TNF-alpha, interleukins-1 and -6, lipid peroxidation, and transaminases. Histologic analysis evaluated intestinal injury using the Chiu muscosal injury score. After I/R, Chiu score in control animals was 3.6 ± 1.2 vs 2.6 ± 0.53 in animals that received bupropion (P < .05). Bupropion pretreatment reduced intestinal. I/R injury and blunted serum elevations of TNF-alpha (0.96 ± 1.1 ng/mL vs 0.09 ± 0.06 ng/mL, P < .05) and interleukin-1 (0.53 ± 0.24 ng/mL vs 0.2 ± 0.11 ng/mL, P < .05). Bupropion in reduced intestinal I/R injury through immunomodulatory machanisms that involve inflammatory cytokines such as TNF-alpha.

Effects of thalidomide and pentoxyphylline over local and remote organ injury after intestinal ischemia/reperfusion.

OBJECTIVE: We investigated the effects of thalidomide alone or in combination with pentoxyphylline upon intestinal ischemia/reperfusion (I/R) injury in the rat. MATERIALS AND METHODS: Twenty male Wistar rats were randomized into 5 groups: sham-operated (SHAM), control (CTL), thalidomide (400 mg/kg) treatment (THAL), pentoxyphylline (50 mg/kg) treatment and a combination group (THAL + POX). I/R was induced by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion. We measured serum concentrations of aspartate-aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-alpha as well as lipid peroxidation and antioxidant status. Intestinal samples were morphologically analyzed, and dry to wet (W/D) ratios calculated in intestinal, lung and liver samples, as a measurement of tissue edema. RESULTS: Serum concentrations of AST, LDH, and TNF-alpha were increased after I/R in the CTL compared with the SHAM group (P < .05). Lipid peroxidation was also increased, and antioxidant capacity in serum, decreased (P < .05). The W/D ratio was elevated in all tissue samples as well (P < .05). Both thalidomide and pentoxyphylline effectively reduced AST, LDH, TNF-alpha, and lipid peroxidation levels, as well as attenuated tissue edema and intestinal injury induced by I/R (P < .05). Combination treatment showed only modest additive effects on lung W/D ratio and TNF-alpha levels. CONCLUSION: Both drugs protected the intestine, lungs, and liver against intestinal I/R injury, probably by inhibition of TNF-alpha and lipid peroxidation. However, combination treatment showed small, additive effects.