Fluoxetine as an antidepressant agent induces directly deleterious effects on rat isolated pancreatic mitochondria: ameliorative role of betanin.

Abstract

It has been shown that fluoxetine is cytotoxic on pancreatic beta-cells via induction of mitochondrial dysfunction and oxidative stress. We investigated the direct effect of fluoxetine on isolated pancreatic mitochondria and evaluate the potential protective effects of betanin and thymoquinone.Mitochondria were isolated from rat pancreas and treated with various concentrations of fluoxetine (10-8000 µM). Then, protective effect of betanin (100-500 µM) and thymoquinone (10-100 µM) on fluoxetine-induced mitochondrial toxicity were studied (60 min). The activity of succinate dehydrogenases (SDH), reactive oxygen species (ROS) formation, mitochondrial swelling, mitochondrial membrane potential (MMP) collapse, malondialdehyde (MDA) production and glutathione level were analysed.Fluoxetine directly caused toxicity in pancreatic isolated mitochondria at concentration of 500 μM and higher. Except MDA and GSH, fluoxetine caused significantly SDH activity reduction, MMP collapse, mitochondrial swelling and ROS formation in pancreatic mitochondria. However, our results showed that only betanin protected fluoxetine-induced mitochondrial dysfunction, while thymoquinone had no impact on mitochondrial toxicity induced by fluoxetine.We can conclude that fluoxetine is directly toxic on pancreas isolated mitochondria, which may be related to its diabetogenic potential in humans. Moreover, our finding suggested that use of betanin may be beneficial for prevention of diabetogenic effect of fluoxetine.