Protective role of hispolon and its derivatives against apoptosis in cortical neurons induced by electromagnetic radiation from 4G mobile phone

Electromagnetic radiation (EMR) from wireless devices, particularly mobile phones, is a potentially growing public health concern. In this study, the neuronal effects of EMR on primary cortical neurons (PCNs) from neonatal rat cerebral cortex and the protective role of hispolon (HIS) and its derivatives were investigated as a measure of cranial exposure during mobile phone use. PCNs were isolated and cultured from day-old neonatal rats, then exposed for 2 h to EMR emitted by a mobile phone operating at a frequency of 2100 MHz with 1.6 W/Kg specific absorption rate (SAR) in call-answered mode treated with HIS and its derivatives. The induction of apoptosis through modulation of pro and anti-apoptotic genes via mitochondrial pathway and the protection by the test compounds was assessed. Pyrazole derivatives decreased apoptosis by modulating the levels of pro and anti-apoptotic genes by reducing the levels of reactive oxygen species (ROS) via mitochondrial damage, which was observed in the EMR exposed PCNs. The pyrazole compounds were found to have antioxidative and anti-apoptotic properties. Thus, the neuroprotective mechanisms of the pyrazole derivatives can be investigated further, which may make them appropriate as lead compounds in developing neuroprotective formulations.

[1]  I. Hasan,et al.  Effect of 2400 MHz mobile phone radiation exposure on the behavior and hippocampus morphology in Swiss mouse model , 2021, Saudi journal of biological sciences.

[2]  M. Islam,et al.  Hematobiochemical and histopathological alterations of kidney and testis due to exposure of 4G cell phone radiation in mice , 2021, Saudi journal of biological sciences.

[3]  H. Rafatpanah,et al.  Long-term exposure to electromagnetic radiation from mobile phones can cause considerable changes in the balance of Bax/Bcl2 mRNA expression in the hippocampus of mice , 2020, Electromagnetic biology and medicine.

[4]  K. Balawender,et al.  The impact of selected modifiable lifestyle factors on male fertility in the modern world , 2020, Central European journal of urology.

[5]  B. Banerjee,et al.  Effect of mobile phone signal radiation on epigenetic modulation in the hippocampus of Wistar rat. , 2020, Environmental research.

[6]  J. Nirala,et al.  Effect of mobile phone radiation on oxidative stress, inflammatory response, and contextual fear memory in Wistar rat , 2020, Environmental Science and Pollution Research.

[7]  M. Goudarzi,et al.  The radio-protective effect of rosmarinic acid against mobile phone and Wi-Fi radiation-induced oxidative stress in the brains of rats , 2020, Pharmacological Reports.

[8]  A. M. Said,et al.  Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors , 2020, Journal of enzyme inhibition and medicinal chemistry.

[9]  A. Volceanov,et al.  Antioxidant Therapies for Neuroprotection—A Review , 2019, Journal of clinical medicine.

[10]  Sareesh Naduvil Narayanan,et al.  Radiofrequency electromagnetic radiation-induced behavioral changes and their possible basis , 2019, Environmental Science and Pollution Research.

[11]  E. Castrén,et al.  Culturing primary neurons from rat hippocampus and cortex , 2018, bioRxiv.

[12]  A. Ardjmand,et al.  Exposure to GSM 900-MHz mobile radiation impaired inhibitory avoidance memory consolidation in rat: Involvements of opioidergic and nitrergic systems , 2018, Brain Research.

[13]  N. V. Balaji,et al.  Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase , 2018, ACS omega.

[14]  A. Azab,et al.  Exposure to Electromagnetic Fields Induces Oxidative Stress and Pathophysiological Changes in the Cardiovascular System , 2017 .

[15]  Howon Lee,et al.  What is 5G? Emerging 5G Mobile Services and Network Requirements , 2017 .

[16]  P. Wang,et al.  Hispolon suppresses metastasis via autophagic degradation of cathepsin S in cervical cancer cells , 2017, Cell Death and Disease.

[17]  Gamze Altun,et al.  Effects of electromagnetic fields exposure on the antioxidant defense system , 2017, Journal of microscopy and ultrastructure.

[18]  G. Altun,et al.  Protective effects of melatonin and omega-3 on the hippocampus and the cerebellum of adult Wistar albino rats exposed to electromagnetic fields , 2017, Journal of microscopy and ultrastructure.

[19]  J. H. Kim,et al.  Activation of autophagy at cerebral cortex and apoptosis at brainstem are differential responses to 835 MHz RF-EMF exposure , 2017, The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology.

[20]  D. Averill-Bates,et al.  Activation of apoptosis signalling pathways by reactive oxygen species. , 2016, Biochimica et biophysica acta.

[21]  M. Galal,et al.  Biochemical and histological studies on adverse effects of mobile phone radiation on rat’s brain , 2016, Journal of Chemical Neuroanatomy.

[22]  J. Chipuk,et al.  Physiological and Pharmacological Control of BAK, BAX, and Beyond. , 2016, Trends in cell biology.

[23]  N. V. Balaji,et al.  Free radical reactions of isoxazole and pyrazole derivatives of hispolon: kinetics correlated with molecular descriptors , 2016, Free radical research.

[24]  S. Dasdag,et al.  The link between radiofrequencies emitted from wireless technologies and oxidative stress , 2016, Journal of Chemical Neuroanatomy.

[25]  U. Lindequist,et al.  Effects of Inonotus hispidus Extracts and Compounds on Human Immunocompetent Cells , 2016, Planta Medica.

[26]  N. A. Ahmed,et al.  The antioxidant effect of Green Tea Mega EGCG against electromagnetic radiation-induced oxidative stress in the hippocampus and striatum of rats , 2016, Electromagnetic biology and medicine.

[27]  S. Gopi,et al.  Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives – A review , 2016, Journal of traditional and complementary medicine.

[28]  N. V. Balaji,et al.  Design, synthesis and in vitro cell-based evaluation of the anti-cancer activities of hispolon analogs. , 2015, Bioorganic & medicinal chemistry.

[29]  B. Zhivotovsky,et al.  Calcium and mitochondria in the regulation of cell death. , 2015, Biochemical and biophysical research communications.

[30]  A. Ravi,et al.  Effect of Low-Intensity Microwave Radiation on Monoamine Neurotransmitters and Their Key Regulating Enzymes in Rat Brain , 2015, Cell Biochemistry and Biophysics.

[31]  Z. Fei,et al.  Resveratrol protects primary cortical neuron cultures from transient oxygen-glucose deprivation by inhibiting MMP-9. , 2014, Molecular medicine reports.

[32]  Weiqiao Deng,et al.  Estrogenic and anti-estrogenic activities of hispolon from Phellinus lonicerinus (Bond.) Bond. et sing. , 2014, Fitoterapia.

[33]  T. Motawi,et al.  Biochemical Modifications and Neuronal Damage in Brain of Young and Adult Rats After Long-Term Exposure to Mobile Phone Radiations , 2014, Cell Biochemistry and Biophysics.

[34]  S. Chandna,et al.  Detection of Low Level Microwave Radiation Induced Deoxyribonucleic Acid Damage Vis-à-vis Genotoxicity in Brain of Fischer Rats , 2013, Toxicology international.

[35]  Amit Kumar Srivastava,et al.  Dimethoxycurcumin-induced cell death in human breast carcinoma MCF7 cells: evidence for pro-oxidant activity, mitochondrial dysfunction, and apoptosis , 2012, Archives of Toxicology.

[36]  Kavindra Kumar Kesari,et al.  900-MHz microwave radiation promotes oxidation in rat brain , 2011, Electromagnetic biology and medicine.

[37]  Stefano Ramat,et al.  Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[38]  Erdinç Devrim,et al.  Effects of mobile phone use on brain tissue from the rat and a possible protective role of vitamin C – a preliminary study , 2010, International journal of radiation biology.

[39]  B. Rao,et al.  Antagonistic effects of Zingerone, a phenolic alkanone against radiation-induced cytotoxicity, genotoxicity, apoptosis and oxidative stress in Chinese hamster lung fibroblast cells growing in vitro. , 2010, Mutagenesis.

[40]  Guan-Jhong Huang,et al.  Analgesic Effects and the Mechanisms of Anti-Inflammation of Hispolon in Mice , 2010, Evidence-based complementary and alternative medicine : eCAM.

[41]  B. Aggarwal,et al.  Bisdemethylcurcumin and structurally related hispolon analogues of curcumin exhibit enhanced prooxidant, anti-proliferative and anti-inflammatory activities in vitro. , 2010, Biochemical pharmacology.

[42]  Minsoo Kim,et al.  Effect of 835 MHz radiofrequency radiation exposure on calcium binding proteins in the hippocampus of the mouse brain , 2010, Brain Research.

[43]  Yuan Wang,et al.  Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons , 2010, Brain Research.

[44]  Jacob Eberhardt,et al.  Increased blood-brain barrier permeability in mammalian brain 7 days after exposure to the radiation from a GSM-900 mobile phone. , 2009, Pathophysiology : the official journal of the International Society for Pathophysiology.

[45]  E. Uz,et al.  The protective effect of caffeic acid phenethyl ester (CAPE) on oxidative stress in rat liver exposed to the 900 MHz electromagnetic field , 2009, Toxicology and industrial health.

[46]  E. Ulukaya,et al.  Effect of Mobile Phone Exposure on Apoptotic Glial Cells and Status of Oxidative Stress in Rat Brain , 2009, Electromagnetic biology and medicine.

[47]  L. Salford,et al.  Histopathological examinations of rat brains after long-term exposure to GSM-900 mobile phone radiation , 2008, Brain Research Bulletin.

[48]  E. Aizenman,et al.  Assessment of Cell Viability in Primary Neuronal Cultures , 2008, Current protocols in neuroscience.

[49]  Yaxuan Sun,et al.  Protective effects of vitamin E against oxidative damage induced by Abeta1-40Cu(II) complexes. , 2007, Acta biochimica et biophysica Sinica.

[50]  P. Knapp,et al.  Exposure to cell phone radiation up-regulates apoptosis genes in primary cultures of neurons and astrocytes , 2007, Neuroscience Letters.

[51]  Fehmi Ozguner,et al.  Melatonin modulates 900 MHz microwave-induced lipid peroxidation changes in rat brain , 2006, Toxicology and industrial health.

[52]  O. Aruoma,et al.  Phenolics as potential antioxidant therapeutic agents: mechanism and actions. , 2005, Mutation research.

[53]  I. Cotgreave,et al.  Biological stress responses to radio frequency electromagnetic radiation: are mobile phones really so (heat) shocking? , 2005, Archives of biochemistry and biophysics.

[54]  Niels Kuster,et al.  Whole-body exposure to 2.45 GHz electromagnetic fields does not alter radial-maze performance in rats , 2004, Behavioural Brain Research.

[55]  Guang-xiong Zhou,et al.  Phelligridins C-F: cytotoxic pyrano[4,3-c][2]benzopyran-1,6-dione and furo[3,2-c]pyran-4-one derivatives from the fungus Phellinus igniarius. , 2004, Journal of natural products.

[56]  S. Kamışlı,et al.  Ginkgo biloba prevents mobile phone-induced oxidative stress in rat brain. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[57]  S. Haldar,et al.  The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death. , 1998, Molecular human reproduction.

[58]  U. Lindequist,et al.  HISPOLON, A YELLOW PIGMENT FROM INONOTUS HISPIDUS , 1996 .

[59]  C. Franceschi,et al.  A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). , 1993, Biochemical and biophysical research communications.

[60]  N. V. Balaji,et al.  Synthesis, screening and docking analysis of hispolon analogs as potential antitubercular agents. , 2017, Bioorganic & medicinal chemistry letters.