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Aortic cross-clamping-induced ischemia-reperfusion (IR) is an important factor in the development of postoperative acute cardiac injury following abdominal aortic surgery. We investigated the possible anti-oxidant/anti-inflammatory effects of fluoxetine (FLX), which is used widely as a preoperative anxiolytic on cardiac injury induced by IR of the infrarenal abdominal aorta. FLX was administered to IR-performed (60 min of ischemia and 120 min of reperfusion) rats for 3 days, once daily at 20 mg/kg i.p. dosage. Results were compared to control and non-FLX-treated IR-performed rats. Serum creatine kinase (CK) and CK-MB levels, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels in the IR group were significantly higher whereas superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels were lower than for the control. IR also increased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1β, and interleukin-6 and decreased interleukin-10 levels. FLX decreased CK, CK-MB, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels while increasing superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels. FLX also decreased myeloperoxidase activity, tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels and increased interleukin-10 levels compared to IR. FLX attenuated the morphological changes associated with cardiac injury. Our study clearly demonstrates that FLX confers protection against aortic IR-induced cardiac injury, tissue leucocyte infiltration, and cellular integrity via its anti-oxidant/anti-inflammatory effects.

Oxidative stress and reperfusion injury may develop in different ischemia-reperfusion (IR) models. Growing evidence links altered lipid protein redox-homeostasis with IR. The effect of fluoxetine (FLX; N-methyl-3-[4-(trifluoromethyl) phenoxy] benzenepropanamine), on the lipid protein redox-homeostasis mechanisms in the rats exposed to aortic IR is unclear. We aimed to investigate the effects of FLX on circulating protein oxidation and lipid peroxidation parameters, such as ischemia modified albumin (IMA), lipid hydroperoxide (LOOH), prooxidant antioxidant balance (PAB), erythrocyte glutathione (GSH), CuZn-superoxide dismutase (CuZn-SOD), ferric reducing antioxidant power (FRAP), as potential IR biomarkers. Wistar rats were randomized into three groups (n=7/group): 1) Control (sham laparotomy); 2) IR without FLX, (60min ischemia and 120min reperfusion); 3) IR with FLX (FLX+IR) (FLX 20mg/kg/day, i.p. for three days before surgery). All of the aforementioned parameters (IMA, LOOH, PAB, GSH, CuZn-SOD, and FRAP) were measured spectrophotometrically. IMA, LOOH, and PAB levels in IR group were significantly higher than the control (P<0.01 respectively) and fluoxetine groups (P<0.01, P<0.01, and P<0.05 respectively), whereas CuZn-SOD activities, GSH and FRAP were significantly lower in IR groups. Fluoxetine group significantly reduced IMA when compared to IR group (P<0.001) and control group (P<0.01). With respect to IMA, LOOH and PAB, impaired redox homeostasis is substantially more prominent in aortic IR. The antidepressant FLX has profitable effects on circulating redox status in rats exposed to aortic IR. FLX administration before IR might decrease the surgery-enhanced free radical production; taken together, the antioxidant effects of FLX supplementation should be considered in future studies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Ischemia-reperfusion (IR) has been reported to be associated with augmented reactive oxygen radicals and cytokines. Currently, we aimed to examine the influence of fluoxetine, which is already used as a preoperative anxiolytic, in the context of IR induced by occlusion of infrarenal abdominal aorta (60 min of ischemia) and its effects on renal oxidative status, inflammation, renal function, and cellular integrity in reperfusion (120 min post-ischemia). Male rats were randomly assigned as control, IR, and pretreated groups. The pretreated group animals received fluoxetine (20 mg/kg, i.p.) once daily for 3 days. Renal tissue oxidative stress, myeloperoxidase activity, proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6), histology, and function were assessed. As an anti-inflammatory cytokine, interleukin-10 was also assessed. IR led to a significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant antioxidant balance and decrease in superoxide dismutase activity and ferric reducing/antioxidant power level (p < 0.05), but fluoxetine was able to restore these parameters. High concentrations of tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase activity caused by IR were significantly decreased in kidney tissue with fluoxetine. In addition, interleukin-10 levels were high in fluoxetine pretreated group. IR resulted in disrupted cellular integrity, infiltration of tissue with leukocytes, and decreased serum creatinine-urea levels (p < 0.05). Fluoxetine significantly restored impaired redox balance and inflammation parameters of rats subjected to IR to baseline values. This beneficial effect of fluoxetine on redox balance might be addressed to an improvement in renal function.

Background: Aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute lung injury after abdominal aortic surgery. The aim of the present study was to examine the effect of fluoxetine (Flx), a selective serotonin reuptake inhibitor widely used as a preoperative anxiolytic, on lung injury induced by abdominal aortic IR in rats., Methods: Wistar rats were randomized into three groups (n = 7 per group): (1) control (sham laparotomy); (2) IR without Flx (60-min ischemia and 120-min reperfusion); (3) IR with Flx (Flx + IR) (Flx 20 mg/kg/d, intraperitoneally for 3 d before surgery). Lung tissue samples and bronchoalveolar lavage (BAL) were obtained for biochemical analysis of oxidative status. Ischemia-modified albumin (IMA) level and protein concentrations in BAL and lung wet to dry weight ratios were determined. Histologic evaluation of the lung tissues was also performed., Results: IR without Flx led to significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant-antioxidant balance and decrease in superoxide dismutase, glutathione, and ferric reducing antioxidant power activities (P < 0.05 versus control), whereas Flx was able to restore these parameters (P > 0.05 versus control) and decrease IMA level (P < 0.01 versus control) and protein concentration (P < 0.05 versus control) in BAL and wet to dry lung weight ratio. Histologic evaluation showed that Flx attenuated the morphologic changes associated with lung injury., Conclusions: The results indicate that Flx confers protection against aortic IR-induced lung oxidative stress and cellular integrity. IMA levels in BAL may be used as a follow-up marker for the efficacy of treatment in lung injury., (Copyright © 2014 Elsevier Inc. All rights reserved.)