j cell neurosci oxid stress

Journal of Cellular Neuroscience and Oxidative Stress

2149-7222

Yasemin NAZIROĞLU

10.37212/jcnos.715227

Neurosciences

Sinirbilim

Levetiracetam modulates hypoxia-induced inflammation and oxidative stress via inhibition of TRPV1 channel in the DBTRG glioblastoma cell line

Ertılav

Kemal

Süleyman Demirel University

04 06 2020

11 3 885 894 11 15 2019 12 18 2019

2008

Journal of Cellular Neuroscience and Oxidative Stress

Hypoxia (HPX) induces mitochondrial oxidative stress, inflammation and apoptosis in brain and neurons. Ca2+ permeable TRPV1 channel is gated by capsaicin and reactive oxygen species (ROS), although its activity was decreased in neurons by antioxidants. LEV has been used as antiepileptic drug in the treatment of epilepsy. LEV inhibited voltage gated calcium channels via its antioxidant property in neurons. Hence, it may modulate HPX-induced ROS, inflammation and apoptosis via inhibition of TRPV1 in the DBTRG cells. The DBTRG glioblastoma cells were divided into four groups as control, LEV (100 µM and 24 hours), and HPX and LEV+HPX. HPX in the cells was induced by using CoCl2 (200 µM and 24 hours). HPX-induced intracellular Ca2+ response to TRPV1 activation was increased in the cells from capsaicin, although it was reduced by the LEV and TRPV1 blocker (capsazepine). LEV treatment improved intracellular Ca2+ responses, mitochondrial function, suppressed the generation of cytokine (IL-1β, and TNF-α) and ROS in the cells. Apoptosis, lipid peroxidation level, caspase -3 and -9 activities were increased in the cells exposed to the HPX, although glutathione peroxidase activity and reduced glutathione level were decreased by the HPX. However, they were modulated in the cells by LEV treatment. In DBTRG neuronal cells exposed to HPX conditions, the neuroprotective effects of LEV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and TRPV1 channel. LEV could be used as an effective agent via modulation of TRPV1 in the treatment of neurodegeneration exposure to HPX.

Apoptosis Hypoxia Inflammation Levetiracetam Oxidative stress TRPV1 channel

Abd El Motteleb DM, Hussein S, Hasan MM, Mosaad H. (2018). Comparison between the effect of human Wharton's jelly-derived mesenchymal stem cells and levetiracetam on brain infarcts in rats. J Cell Biochem. 119(12):9790-9800.

Abdel-Wahab BA, Shaikh IA, Khateeb MM, Habeeb SM. (2015). Omega 3 polyunsaturated fatty acids enhance the protective effect of levetiracetam against seizures, cognitive impairment and hippocampal oxidative DNA damage in young kindled rats. Pharmacol Biochem Behav. 135:105-113.

Akpınar H, Nazıroğlu M, Övey İS, Çiğ B, Akpınar O. (2016). The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels. Sci Rep. 6:37196.

Angehagen M, Margineanu DG, Ben-Menachem E, Rönnbäck L, Hansson E, Klitgaard H. (2003). Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons. Neuroreport 14(3):471-475.

Ataizi ZS, Ertilav K, Nazıroğlu M. (2019). Mitochondrial oxidative stress-induced brain and hippocampus apoptosis decrease through modulation of caspase activity, Ca(2+) influx and inflammatory cytokine molecular pathways in the docetaxel-treated mice by melatonin and selenium treatments. Metab Brain Dis. 34(4):1077-1089.

Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(6653):816-24.

Cheng BC, Chen JT, Yang ST, Chio CC, Liu SH, Chen RM. (2017). Cobalt chloride treatment induces autophagic apoptosis in human glioma cells via a p53-dependent pathway. Int J Oncol. 50(3):964-974.

Clapham DE. (2003). TRP channels as cellular sensors. Nature 426(6966):517-524.

Costa C, Martella G, Picconi B, Prosperetti C, Pisani A, Di Filippo M, Pisani F, Bernardi G, Calabresi P. (2006). Multiple mechanisms underlying the neuroprotective effects of antiepileptic drugs against in vitro ischemia. Stroke. 37(5):1319-1326.

Dai Z, Xiao J, Liu SY, Cui L, Hu GY, Jiang DJ. (2008). Rutaecarpine inhibits hypoxia/reoxygenation-induced apoptosis in rat hippocampal neurons. Neuropharmacology. 55(8):1307-1312.

Deveci HA, Akyuva Y, Nur G, Nazıroğlu M. (2019). Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line. Biomed Pharmacother. 111:292-304.

Ertilav K, Nazıroğlu M, Ataizi ZS, Braidy N. (2019). Selenium enhances the apoptotic efficacy of docetaxel through activation of TRPM2 channel in DBTRG glioblastoma cells. Neurotox Res. 35(4):797-808.

Ertilav K, Uslusoy F, Ataizi S, Nazıroğlu M. (2018). Long term exposure to cell phone frequencies (900 and 1800 MHz) induces apoptosis, mitochondrial oxidative stress and TRPV1 channel activation in the hippocampus and dorsal root ganglion of rats. Metab Brain Dis. 33(3):753-763.

Ertilav K. (2019). Pregabalin protected cisplatin-induced oxidative neurotoxicity in neuronal cell line. J Cell Neurosci Oxid Stress. 11 (1): 815-824.

Ibi M, Matsuno K, Shiba D, Katsuyama M, Iwata K, Kakehi T, Nakagawa T, Sango K, Shirai Y, Yokoyama T, Kaneko S, Saito N, Yabe-Nishimura C. (2008). Reactive oxygen species derived from NOX1/NADPH oxidase enhance inflammatory pain. J Neurosci. 28(38):9486-9494.

Imai T, Sugiyama T, Iwata S, Nakamura S, Shimazawa M, Hara H. (2020). Levetiracetam, an antiepileptic drug has neuroprotective effects on intracranial hemorrhage injury. Neuroscience. 431:25-33.

Joshi DC, Bakowska JC. (2011). Determination of mitochondrial membrane potential and reactive oxygen species in live rat cortical neurons. J Vis Exp 51: 2704.

Kaur C, Rathnasamy G, Ling EA. (2013). Roles of activated microglia in hypoxia induced neuroinflammation in the developing brain and the retina. J Neuroimmune Pharmacol. 8(1):66-78.

Keil VC, Funke F, Zeug A, Schild D, Müller M. (2011). Ratiometric high-resolution imaging of JC-1 fluorescence reveals the subcellular heterogeneity of astrocytic mitochondria. Pflugers Arch. 462:693-708.

Khan MSS, Asif M, Basheer MKA, Kang CW, Al-Suede FS, Ein OC, Tang J, Majid ASA, Majid AMSA. (2017). Treatment of novel IL17A inhibitor in glioblastoma implementing 3rd generation co-culture cell line and patient-derived tumor model. Eur J Pharmacol. 803:24-38.

Komur M, Okuyaz C, Celik Y, Resitoglu B, Polat A, Balci S, Tamer L, Erdogan S, Beydagi H. (2014). Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats. Childs Nerv Syst. 30(6):1001-1009.

Kumar VS, Gopalakrishnan A, Nazıroğlu M, Rajanikant GK. (2014). Calcium ion--the key player in cerebral ischemia. Curr Med Chem. 21(18):2065-2075.

Lawrence RA, Burk RF. (1976). Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952-958.

Lukyanetz EA, Shkryl VM, Kostyuk PG. (2002). Selective blockade of N-type calcium channels by levetiracetam. Epilepsia. 43(1):9-18.

Meehan AL, Yang X, McAdams BD, Yuan L, Rothman SM. (2011). A new mechanism for antiepileptic drug action: vesicular entry may mediate the effects of levetiracetam. J Neurophysiol. 106(3):1227-1239.

Muñoz-Sánchez J, Chánez-Cárdenas ME. (2019). The use of cobalt chloride as a chemical hypoxia model. J Appl Toxicol. 39(4):556-570.

Nazıroğlu M. (2007). New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res. 32(11):1990-2001.

Nazıroğlu M. (2012). Molecular role of catalase on oxidative stress-induced Ca(2+) signaling and TRP cation channel activation in nervous system. J Recept Signal Transduct Res. 32(3):134-141.

Placer ZA, Cushman L, Johnson BC. (1966). Estimation of products of lipid peroxidation (malonyl dialdehyde) in biological fluids. Anal Biochem 16:359-364.

Sedlak J, Lindsay RHC. (1968). Estimation of total, protein bound and non-protein sulfhydryl groups in tissue with Ellmann' s reagent. Anal Biochem 25:192-205.

Stettner M, Dehmel T, Mausberg AK, Köhne A, Rose CR, Kieseier BC. (2011). Levetiracetam exhibits protective properties on rat Schwann cells in vitro. J Peripher Nerv Syst. 16(3):250-260.

Sun Z, Han J, Zhao W, Zhang Y, Wang S, Ye L, Liu T, Zheng L. (2014). TRPV1 activation exacerbates hypoxia/reoxygenation-induced apoptosis in H9C2 cells via calcium overload and mitochondrial dysfunction. Int J Mol Sci. 15(10):18362-18380.

Thornton C, Leaw B, Mallard C, Nair S, Jinnai M, Hagberg H. (2017). Cell death in the developing brain after hypoxia-ischemia. Front Cell Neurosci. 11:248.

Ureshino RP, Erustes AG, Bassani TB, Wachilewski P, Guarache GC, Nascimento AC, Costa AJ, Smaili SS, Pereira GJDS. (2019). The Interplay between Ca(2+) signaling pathways and neurodegeneration. Int J Mol Sci. 20(23): pii: E6004.

Vogl C, Mochida S, Wolff C, Whalley BJ, Stephens GJ. The synaptic vesicle glycoprotein 2A ligand levetiracetam inhibits presynaptic Ca2+ channels through an intracellular pathway. Mol Pharmacol. 82(2):199-208.

Yang XL, Wang X, Shao L, Jiang GT, Min JW, Mei XY, He XH, Liu WH, Huang WX, Peng BW. (2019). TRPV1 mediates astrocyte activation and interleukin-1β release induced by hypoxic ischemia (HI). J Neuroinflammation. 16(1):114.

Zhao XY, Lu MH, Yuan DJ, Xu DE, Yao PP, Ji WL, Chen H, Liu WL, Yan CX, Xia YY, Li S, Tao J, Ma QH. (2019). Mitochondrial dysfunction in neural injury. Front Neurosci. 13:30.