Effects of The Antidepressant Venlafaxine on The Expression of Peroxiredoxin-3 and Peroxiredoxin-5 Against LPS-induced Oxidative Stress in SHSY-5Y Neurons.

Abstract

The main objective of this study was to examine the potential neuroprotective properties of venlafaxine, an antidepressant belonging to the serotonin-norepinephrine reuptake inhibitor class. Furthermore, it provides a novel insight into how venlafaxine might interact with peroxiredoxin-3 and -5 enzymes (PRDX-3 and PRDX-5), pivotal cellular antioxidant defence system components. For this purpose, human neuroblastoma (SHSY-5Y) cells were pretreated with venlafaxine (0-100 µM) for 12 h, followed by a 4 h LPS exposure (1 µg/mL) to induce oxidative stress. Cell viability was determined by MTT assay, and ROS generation was assessed by DCFH-DA assay. Protein and mRNA expression levels of PRDX-3 and PRDX-5 were determined by immunoblotting and RT-PCR, respectively. Based on the results obtained, it was found that the venlafaxine pre-treatment led to a notable reduction in intracellular ROS accumulation induced by LPS when compared to the control group (p< 0.05). In the same manner, it was observed that venlafaxine pre-treatment altered LPS-induced PRDX-3 and PRDX-5 expression in neuronal cells (p< 0.05). Our findings indicate the involvement of multifunctional PRDX-3 and PRDX-5 enzymes in the antioxidant effect of venlafaxine and suggest that further investigations into this pathway could provide valuable therapeutic contributions.