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

Year 2024, Issue: Special Issue / International Multidisciplinary Symposium on Drug Research and Development, DRD-2023, 17 - 26, 01.07.2024

Fadime Aydın Köse Muhammed İsmail Akgül Ayçe İdil Arap

https://doi.org/10.52794/hujpharm.1368308

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 cells (SH-SY5Y) 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 qRT-PCR, respectively.
Based on the results obtained, it was found that the venlafaxine pretreatment
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.

Keywords

Venlafaxine, Peroxiredoxin-3, Peroxiredoxin-5, Oxidative Stress, Antioxidant

Ethical Statement

In this study, no experiment was conducted with animal or human samples that would require ethical approval.

Supporting Institution

This study received financial support from the TUBİTAK Research Project Support Programme for Undergraduate Students (2209-A 2021/1).

Thanks

The authors would like to express their gratitude for their valuable criticize to Prof. Sinem Ezgi TURUNÇ ÖZOĞLU.

SHSY-5Y Nöronlarında LPS ile İndüklenen Oksidatif Stres Artışında Antidepresan Venlafaksin'in Peroksiredoksin-3 ve Peroksiredoksin-5 Ekspresyonları Üzerindeki Etkileri

Abstract

Bu çalışmanın temel amacı, serotonin-norepinefrin geri alım inhibitörü bir antidepresan olan venlafaksinin potansiyel nöroprotektif özelliklerini incelemektir. Ayrıca, venlafaksinin hücresel antioksidan savunma sisteminin önemli bileşenleri olan peroksirodoksin-3 ve -5 (PRDX-3 and PRDX-5) enzimleriyle olası etkileşimine dair yeni bir bakış açısı sunmaktadır. Bu amaçla, insan nöroblastoma (SHSY-5Y) hücreleri, 12 saat venlafaksin (0-100 µM) ile muamele edildikten sonra oksidatif stresi indüklemek için 4 saat LPS (1 µg/mL) ile inkübe edildiler. Hücre canlılığı MTT testi ile belirlendi ve ROS oluşumu DCFH-DA testi ile değerlendirildi. PRDX-3 ve PRDX-5 protein ve mRNA ifade seviyeleri sırasıyla immunoblotlama ve RT-PCR ile belirlendi. Elde edilen sonuçlara göre, hücrelerde kontrol grubuna göre venlafaksin uygulamasın LPS ile indüklenen hücresel ROT birikiminde belirgin bir azalmaya yol açtığı tespit edilmiştir (p <0.05). Benzer olarak, venlafaksin ön işlemi, nöronal hücrelerde LPS tarafından indüklenen PRDX-3 ve PRDX-5 ifadesini değiştirdiği gözlenmiştir (p <0.05). Elde edilen bu bulgular, venlafaksinin antioksidan etkisinde multifonksiyonel PRDX-3 ve PRDX-5 enzimlerinin rol oynadığına işaret etmekte olup bu yolak ile ilişkili yapılacak ileri çalışmaların önemli terapötik katkılarda bulunabileceğini düşündürmektedir.

Keywords

Venlafaksin, Peroksiredoksin-3, Peroksiredoksin-5, Oksidatif stres, Antioksidan

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