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OBJECTIVE(S): Due to cross-clamping of the aorta during aortic aneurysm surgeries, ischemia-reperfusion (IR) develops, and it may cause damage to aorta itself or even to remote organs by oxidative stress or inflammation. Fluoxetine (FLX) which might be used in the preoperative period for its tranquilizing effect also has antioxidant effects in short-term use. The purpose of our study is to examine whether FLX protects aorta tissue, against the damage caused by IR.METHODS: 3 groups of Wistar rats formed randomly. 1) Control group (sham-operated), 2) IR group (60 min. ischemia+120 min. perfusion), 3) FLX+IR group (FLX dose was 20 mg/kg for 3 days i.p. before IR). At the end of each procedure, aorta samples were collected, and oxidant-antioxidant, anti-inflammatory, and anti-apoptotic status of the aorta were evaluated. Histological examinations of the samples were provided. RESULTS: Levels of LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1β, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA were found to be significantly increased in the IR group compared to control (p<0.05) and the SOD, GSH, TAS, and IL-10 levels were significantly lower (p<0.05). FLX significantly decreased LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1β, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA levels in the FLX+IR group compared to IR group (p<0.05) and increased IL-10, SOD, GSH, and TAS (p<0.05). FLX administration prevented the deterioration of aortic tissue damage.CONCLUSION: Our study is the first study that demonstrates FLX mediated suppression of IR injury in the infrarenal abdominal aorta by antioxidant, anti-inflammatory, and anti-apoptotic properties.