Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide

Abstract

Abstract. Oxidative stress and reactive oxygen species generation have been implicated in the pathogenesis of several neurological disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. In the present study, the neuroprotective effects of selegiline against hydrogen peroxide-induced oxidative stress in hippocampus-derived neural stem cells (NSCs) were evaluated. NSCs isolated from neonatal Wistar rats were pretreated with different doses of selegiline for 48 h and then exposed to 125 µM H 2 O 2 for 30 min. Using MTT and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, acridine orange/ethidium bromide staining and reverse transcription-quantitative polymerase chain reaction, the effects of selegiline on cell survival, apoptosis and the expression of B-cell lymphoma 2 (Bcl-2) and heat shock protein 4 (Hspa4) in pretreated stem cells were assessed compared with a control group lacking pretreatment. The results indicated that the viability of cells pretreated with 20 µM selegiline was significantly increased compared with the control group (P<0.05). Additionally, 20 µM selegiline increased the mRNA expression of Bcl-2 and Hspa4 (P<0.05 vs. control) and suppressed oxidative stress-induced cell death (apoptosis and necrosis; P<0.05 vs. control and 10 µM groups). From these findings, it was concluded that selegiline may be a therapeutic candidate for the treatment of neurological diseases mediated by oxidative stress. IntroductionThe most common neorodegenerative disorders, namely Alzheimer's disease (AD) and Parkinson's disease (PD), are prevalent in ~1% of individuals aged 60 years and older (1). Their etiologies remain uncertain, though there are a number of established pathogenic factors, including oxidative stress, neural apoptosis, mitochondrial dysfunction, excitotoxicity, impairment of the ubiquitin-proteasome system and inflammation (2,3). Neuroprotective therapy has been suggested to prevent disease progression by inhibiting the action of pathogenic factors, for instance, by reducing the production of reactive oxygen species (ROS) (4). Overproduction of ROS may cause oxidative damage to biomolecules and subsequently DNA damage, ultimately leading to the development of neurodegenerative diseases. According to studies on PD, inhibitors of type B monoamine oxidase (MAO), including selegiline [also known as (-)-deprenyl] and rasagiline, are among the most promising neuroprotective agents identified to date (5-7). MAO exists in two forms, MAO-A and -B. The catalytic activity of these enzymes generates H 2 O 2 and nitrogen species, which are toxic products that may cause oxidative damage to mitochondrial DNA (mtDNA) and thus have potential implications for apoptosis, aging and neurodegenerative processes (8). The MAO-B inhibitor, selegiline, is typically recommended as a first-line treatment for PD and has been demonstrated to possess neuroprotective functions (9); notably, this inhibitor protected neuronal cells against induc...

Deprenyl reduces inflammation during acute SIV infection

“…Some data show monoamine oxidase inhibitors (MAOI) have pleiotropic effects that are not well defined ( Kitani et al., 2001 ; Szoko et al., 2018 ) and which may be unrelated to monoamine oxidase inhibition ( Koutsilieri et al., 1996 ; Kragten et al., 1998 ; Lieb, 1983 ; Nagatsu and Sawada, 2006 ; Ryu et al., 2018 ; Tabakman et al., 2004 ; Tatton et al., 1994 ). In animal models, these overlapping effects include regulation of inflammation and reactive oxygen species (ROS) ( Bekesi et al., 2012 ; Bielecka et al., 2010 ; Morsali et al., 2013 ; Nagy et al., 2018 ; Tsao et al., 2014 ), alterations in gene expression ( Tatton and Chalmers-Redman, 1996 ; Tatton et al., 1996 ), increasing longevity ( Kitani et al., 1994 , 1998 ; Knoll and Miklya, 2016 ), and promoting neurite outgrowth and neuronal survival ( Abdanipour et al., 2018 ; Ebadi et al., 2002 ; Koutsilieri et al., 1994 ; Kragten et al., 1998 ; Morsali et al., 2013 ; Tazik et al., 2009 ). In the rodent heart, inhibiting monoamine oxidases reduces inflammation and endothelial dysfunction in the aorta ( Ratiu et al., 2018 ; Sturza et al., 2013 ), decreasing ROS and preventing mitochondrial dysfunction and ER stress in diabetic cardiomyopathy ( Deshwal et al., 2018 ).…”

Water-Soluble, Alanine-Modified Fullerene C60 Promotes the Proliferation and Neuronal Differentiation of Neural Stem Cells

“…H 2 O 2 has widely been used to induce cellular oxidative stress in different cell lines. Previous studies have revealed that cultured NSCs are sensitive to the oxidative stress induced by H 2 O 2 [ 48 , 49 , 50 , 51 , 52 ]. In this study, the activity of antioxidant enzymes (GSH-Px and SOD) and the content of GSH in NSCs reduced after treatment with H 2 O 2 .…”

Low Dose Betahistine in Combination With Selegiline Increases Cochlear Blood Flow in Guinea Pigs

“… 41 Therefore, adjunct therapy with a MAO inhibitor like selegiline may have additional therapeutic benefits, as cochlear tissue might be protected. A study by Abdanipour et al 42 demonstrated the protective effects of selegiline in nervous tissue in vitro. Their experiment showed a significant decrease in apoptosis and necrosis in cells under oxidative stress, when pretreated with selegiline.…”