Remote myocardial injury: the protective role of fluoxetine

Abstract

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.

Opportunities for Drug Repurposing of Serotonin Reuptake Inhibitors: Potential Uses in Inflammation, Infection, Cancer, Neuroprotection, and Alzheimer’s Disease Prevention

“…SSRIs may also have protective effects in developing ischemic heart disease due to their influence on platelet reactivity and inflammatory markers 12 and insulin sensitivity. Fluoxetine was shown to decrease inflammatory markers including IL-1B, IL-6, CK, CK-MB, lipid hydroperoxide, and improved antioxidant balance following aortic cross-clamping reperfusion injury in one animal study 26 , and reduced inflammation and oxidative stress in an animal model of kidney injury 27 . Paroxetine was shown to selectively inhibit G protein-coupled receptor kinase 2 (GRK2), which increases contractility in isolated cardiomyocytes and is a potential target for heart failure therapy 28 .…”

Pathophysiological Mechanisms and Pharmaceutical Interventions of Myocardial Infarction with Depression

“…In a small, randomized, double-blind placebo-controlled trial, the antidepressant fluoxetine was shown to be effective in the treatment of major MDD for three months after AMI [59]. The mechanism of fluoxetine action may be antioxidant and anti-inflammatory [60]. Another randomized, double-blind, placebocontrolled study in patients with AMI found that paroxetine improves cardiac function after AMI by inhibiting G protein-coupled receptor kinase 2 (GRK2), and it is also a widely used antidepressant [61].…”