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Volume 18, Issue 3
  • ISSN: 2212-7968
  • E-ISSN: 1872-3136
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Abstract

Introduction

The brain is highly susceptible to oxidative damage due to excessive oxygen tension, a high concentration of oxidizable substrates, and low antioxidant capacity. Consequently, oxidative stress is linked to several brain disorders and neurodegeneration. Sodium azide is a cytochrome oxidase inhibitor that promotes neurodegeneration by enhancing the release of excitotoxins and inducing oxidative stress through the peroxidation of membrane lipids. This process results in the release of intra-mitochondrial Ca+2 and HO (ROS Dependent-Ca+2 release). Agmatine, a biogenic amine, is also referred to as a free radical scavenger, protecting the brain from membrane collapse, apoptosis, and mitochondrial swelling.

Objective

This study was designed to identify the antioxidative effects of agmatine on sodium azide-induced oxidative stress in brain tissues.

Methodology

Twenty-four male albino Wistar rats were allocated into two groups: a control group receiving water and a test group administered sodium azide (5 mg/kg, intraperitoneally) for a duration of 14 days. Subsequently, the animals were further subdivided and treated for an additional two weeks with either water or agmatine (100 mg/kg). Behavioral assessments were performed one-hour post-agmatine administration, and brain homogenates were prepared for biochemical analyses.

Results

The agmatine-treated group exhibited a significant increase (<0.01) in both the number of entries and the time spent in the light box and the open arms of the light/dark transition box and elevated plus maze tests, respectively. Additionally, agmatine administration significantly enhanced (<0.01) the total number of squares crossed in the open field test. Biochemical assessments revealed that agmatine treatment significantly reduced (<0.01) the levels of reactive oxygen species and malondialdehyde. Moreover, it significantly increased (<0.01) the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and glutathione compared to the control group.

Conclusion

The present study revealed that agmatine has substantial effects on oxidative and antioxidant enzyme levels in sodium azide-induced oxidative stress. Agmatine-treated rats exhibited decreased reactive oxygen species levels and improvements in behavioral impairments resulting from sodium azide administration.

© 2024 Bentham Science Publishers
© 2024 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-03-07

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References

  1. CobleyJ.N. FiorelloM.L. BaileyD.M. 13 reasons why the brain is susceptible to oxidative stress.Redox Biol.20181549050310.1016/j.redox.2018.01.00829413961
     [Google Scholar]
  2. Sharifi-RadM. Anil KumarN.V. ZuccaP. VaroniE.M. DiniL. PanzariniE. RajkovicJ. Tsouh FokouP.V. AzziniE. PelusoI. Prakash MishraA. NigamM. El RayessY. BeyrouthyM.E. PolitoL. IritiM. MartinsN. MartorellM. DoceaA.O. SetzerW.N. CalinaD. ChoW.C. Sharifi-RadJ. Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases.Front. Physiol.20201169410.3389/fphys.2020.0069432714204
     [Google Scholar]
  3. SantosP. HerrmannA.P. ElisabetskyE. PiatoA. Anxiolytic properties of compounds that counteract oxidative stress, neuroinflammation, and glutamatergic dysfunction: A review.Br. J. Psychiatry201941216817810.1590/1516‑4446‑2018‑000530328963
     [Google Scholar]
  4. PadurariuM. AntiochI. BalmusI. CiobicaA. El-LetheyH.S. KamelM.M. Describing some behavioural animal models of anxiety and their mechanistics with special reference to oxidative stress and oxytocin relevance.Int. J. Vet. Sci. Med.2017529810410.1016/j.ijvsm.2017.08.00330255057
     [Google Scholar]
  5. AboutERSH-DB 2011Available from: https://www.cdc.gov/niosh/ershdb/about.html
  6. ZuoY. HuJ. XuX. GaoX. WangY. ZhuS. Sodium azide induces mitochondria mediated apoptosis in PC12 cells through Pgc 1α associated signaling pathway.Mol. Med. Rep.20191932211221910.3892/mmr.2019.985330664159
     [Google Scholar]
  7. Van LaarV.S. RoyN. LiuA. RajprohatS. ArnoldB. DukesA.A. HolbeinC.D. BermanS.B. Glutamate excitotoxicity in neurons triggers mitochondrial and endoplasmic reticulum accumulation of Parkin, and, in the presence of N-acetyl cysteine, mitophagy.Neurobiol. Dis.20157418019310.1016/j.nbd.2014.11.01525478815
     [Google Scholar]
  8. DukoffD.J. HoggD.W. HawrsyhP.J. BuckL.T. Scavenging ROS dramatically increases NMDA receptor whole cell currents in painted turtle cortical neurons. J. Exp. Biol., 2014217Pt 18jeb.10582510.1242/jeb.10582525063855
     [Google Scholar]
  9. ChenT. YangY. LuoP. LiuW. DaiS. ZhengX. FeiZ. JiangX. Homer1 knockdown protects dopamine neurons through regulating calcium homeostasis in an in vitro model of Parkinson’s disease.Cell. Signal.201325122863287010.1016/j.cellsig.2013.09.00424036210
     [Google Scholar]
  10. NöldnerM. Oral treatment with the Ginkgo biloba extract EGb 761® prevents sodium azide-induced memory deficits in rats.Planta Medica Int. Open20174S 01S1S20210.1055/s‑0037‑1608413
     [Google Scholar]
  11. AhmedM.A.E. Farouk FahmyH. Histological study on the effect of sodium azide on the corpus striatum of albino rats and the possible protective role of L-carnitine.Egypt. J. Histol.2013361394910.1097/01.EHX.0000424089.76006.d7
     [Google Scholar]
  12. OlajideO.J. AkinolaB.O. AjaoS.M. EnaibeB.U. Sodium azide-induced degenerative changes in the dorsolateral prefrontal cortex of rats: Attenuating mechanisms of kolaviron.Eur. J. Anat.20162014764
     [Google Scholar]
  13. Delgado-CortésM.J. Espinosa-OlivaA.M. SarmientoM. ArgüellesS. HerreraA.J. MauriñoR. VillaránR.F. VeneroJ.L. MachadoA. de PablosR.M. Synergistic deleterious effect of chronic stress and sodium azide in the mouse hippocampus.Chem. Res. Toxicol.201528465166110.1021/tx500440825658758
     [Google Scholar]
  14. IlesanmiO. InalaM. RidwanA. Neuroprotective effect of ethylacetate fraction of Antiaris africana against sodium azide-induced neurotoxicity in the striata of male wistar rats.Iran. J. Toxicol.20231741810.61186/IJT.17.4.1
     [Google Scholar]
  15. MolderingsG.J. HaenischB. Agmatine (decarboxylated l-arginine): Physiological role and therapeutic potential.Pharmacol. Ther.2012133335136510.1016/j.pharmthera.2011.12.00522212617
     [Google Scholar]
  16. KotagaleN. DixitM. GarmelwarH. BhondekarS. UmekarM. TaksandeB. Agmatine reverses memory deficits induced by Aβ1–42 peptide in mice: A key role of imidazoline receptors.Pharmacol. Biochem. Behav.202019617297610.1016/j.pbb.2020.17297632598984
     [Google Scholar]
  17. KotagaleN.R. TaksandeB.G. InamdarN.N. Neuroprotective offerings by agmatine.Neurotoxicology20197322824510.1016/j.neuro.2019.05.00131063707
     [Google Scholar]
  18. Sirvanci-YalabikM. SehirliA.O. UtkanT. AriciogluF. Agmatine, a metabolite of arginine, improves learning and memory in streptozotocin-induced Alzheimer’s disease model in rats.Klinik Psikofarmakol. BBülteni201626434235410.5455/bcp.20161121125642
     [Google Scholar]
  19. KotagaleN. BhondekarS. BhadM. PiseS. CharpeA. UmekarM. TaksandeB. Agmatine prevents development of tolerance to anti-nociceptive effect of ethanol in mice.Alcohol20221011810.1016/j.alcohol.2022.02.00435227825
     [Google Scholar]
  20. OstovanV.R. AmiriZ. MoeziL. PirsalamiF. EsmailiZ. MoosaviM. The effects of subchronic agmatine on passive avoidance memory, anxiety-like behavior and hippocampal Akt/GSK-3β in mice.Behav. Pharmacol.2022331425010.1097/FBP.000000000000066634954711
     [Google Scholar]
  21. FreitasA.E. EgeaJ. BuendiaI. Gómez-RangelV. ParadaE. NavarroE. CasasA.I. WojniczA. OrtizJ.A. CuadradoA. Ruiz-NuñoA. RodriguesA.L.S. LopezM.G. Agmatine, by improving neuroplasticity markers and inducing Nrf2, prevents corticosterone-induced depressive-like behavior in mice.Mol. Neurobiol.20165353030304510.1007/s12035‑015‑9182‑625966970
     [Google Scholar]
  22. El-SayedE.K. AhmedA.A.E. MorsyE.M.E. NofalS. Neuroprotective effect of agmatine (decarboxylated >l -arginine) against oxidative stress and neuroinflammation in rotenone model of Parkinson’s disease.Hum. Exp. Toxicol.201938217318410.1177/096032711878813930001633
     [Google Scholar]
  23. BattagliaV. GrancaraS. SatrianoJ. SaccoccioS. AgostinelliE. ToninelloA. Agmatine prevents the Ca2+-dependent induction of permeability transition in rat brain mitochondria.Amino Acids201038243143710.1007/s00726‑009‑0402‑020012118
     [Google Scholar]
  24. CondelloS. CurròM. FerlazzoN. CaccamoD. SatrianoJ. IentileR. Agmatine effects on mitochondrial membrane potential andNF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells.J. Neurochem.20111161677510.1111/j.1471‑4159.2010.07085.x21044082
     [Google Scholar]
  25. AgostinelliE. MarquesM.P.M. CalheirosR. GilF.P.S.C. TemperaG. ViceconteN. BattagliaV. GrancaraS. ToninelloA. Polyamines: Fundamental characters in chemistry and biology.Amino Acids201038239340310.1007/s00726‑009‑0396‑720013011
     [Google Scholar]
  26. FarhanM. RafiH. RafiqH. SiddiquiF. KhanR. AnisJ. Study of mental illness in rat model of sodium azide induced oxidative stress.J. Pharm. Nutr. Sci.20199421322110.29169/1927‑5951.2019.09.04.3
     [Google Scholar]
  27. ArrantA.E. Schramm-SapytaN.L. KuhnC.M. Use of the light/dark test for anxiety in adult and adolescent male rats.Behav. Brain Res.201325611912710.1016/j.bbr.2013.05.03523721963
     [Google Scholar]
  28. KraeuterA.K. GuestP.C. SarnyaiZ. The elevated plus maze test for measuring anxiety-like behavior in rodents. Pre-Clinical Models. GuestP. New YorkHumana Press2019697410.1007/978‑1‑4939‑8994‑2_4
     [Google Scholar]
  29. SeibenhenerM.L. WootenM.C. Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J. Vis. Exp.20159696e52434[Journal of Visualized Experiments]25742564
     [Google Scholar]
  30. CathcartR. SchwiersE. AmesB.N. Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein assay.Anal. Biochem.1983134111111610.1016/0003‑2697(83)90270‑16660480
     [Google Scholar]
  31. OhkawaH. OhishiN. YagiK. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal. Biochem.197995235135810.1016/0003‑2697(79)90738‑336810
     [Google Scholar]
  32. KakkarP. DasB. ViswanathanP.N. A modified spectrophotometric assay of superoxide dismutase.Indian J. Biochem. Biophys.198421130132
     [Google Scholar]
  33. SinhaA.K. Colorimetric assay of catalase.Anal. Biochem.197247238939410.1016/0003‑2697(72)90132‑74556490
     [Google Scholar]
  34. EllmanG.L. Tissue sulfhydryl groups.Arch. Biochem. Biophys.1959821707710.1016/0003‑9861(59)90090‑613650640
     [Google Scholar]
  35. MohandasJ. MarshallJ.J. DugginG.G. HorvathJ.S. TillerD.J. Differential distribution of glutathione and glutathione-related enzymes in rabbit kidney.Biochem. Pharmacol.198433111801180710.1016/0006‑2952(84)90353‑86145422
     [Google Scholar]
  36. Winiarska-MieczanA. Baranowska-WójcikE. KwiecieńM. GrelaE.R. SzwajgierD. KwiatkowskaK. KiczorowskaB. The role of dietary antioxidants in the pathogenesis of neurodegenerative diseases and their impact on cerebral oxidoreductive balance.Nutrients202012243510.3390/nu1202043532046360
     [Google Scholar]
  37. XuW. GaoL. LiT. ShaoA. ZhangJ. Neuroprotective role of agmatine in neurological diseases.Curr. Neuropharmacol.20181691296130510.2174/1570159X1566617080812063328786346
     [Google Scholar]
  38. van VelzenL.S. WijdeveldM. BlackC.N. van TolM.J. van der WeeN.J.A. VeltmanD.J. PenninxB.W.J.H. SchmaalL. Oxidative stress and brain morphology in individuals with depression, anxiety and healthy controls.Prog. Neuropsychopharmacol. Biol. Psychiatry20177614014410.1016/j.pnpbp.2017.02.01728249819
     [Google Scholar]
  39. BlackC.N. BotM. SchefferP.G. PenninxB.W.J.H. Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort.Psychol. Med.201747593694810.1017/S003329171600282827928978
     [Google Scholar]
  40. MillerM.W. LinA.P. WolfE.J. MillerD.R. Oxidative stress, inflammation, and neuroprogression in chronic PTSD.Harv. Rev. Psychiatry2018262576910.1097/HRP.000000000000016729016379
     [Google Scholar]
  41. BhattS. NagappaA.N. PatilC.R. Role of oxidative stress in depression.Drug Discov. Today20202571270127610.1016/j.drudis.2020.05.00132404275
     [Google Scholar]
  42. CorreiaA.S. CardosoA. ValeN. Oxidative stress in depression: The link with the stress response, neuroinflammation, serotonin, neurogenesis and synaptic plasticity.Antioxidants202312247010.3390/antiox1202047036830028
     [Google Scholar]
  43. FilipovićD. TodorovićN. BernardiR.E. GassP. Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms.Brain Struct. Funct.2017222112010.1007/s00429‑016‑1218‑927033097
     [Google Scholar]
  44. AtroozF. AlkadhiK.A. SalimS. Understanding stress: Insights from rodent models.Curr. Res. Neurobiol.2021210001310.1016/j.crneur.2021.10001336246514
     [Google Scholar]
  45. RafiH. RafiqH. FarhanM. Inhibition of NMDA receptors by agmatine is followed by GABA/glutamate balance in benzodiazepine withdrawal syndrome.Beni. Suef Univ. J. Basic Appl. Sci.202110113
     [Google Scholar]
  46. JinH. KanthasamyA. GhoshA. AnantharamV. KalyanaramanB. KanthasamyA.G. Mitochondria-targeted antioxidants for treatment of Parkinson’s disease: Preclinical and clinical outcomes.Biochim. Biophys. Acta Mol. Basis Dis.2014184281282129410.1016/j.bbadis.2013.09.00724060637
     [Google Scholar]
  47. SinghA. KukretiR. SasoL. KukretiS. Oxidative stress: A key modulator in neurodegenerative diseases.Molecules2019248158310.3390/molecules2408158331013638
     [Google Scholar]
  48. CollinF. Chemical basis of reactive oxygen species reactivity and involvement in neurodegenerative diseases.Int. J. Mol. Sci.20192010240710.3390/ijms2010240731096608
     [Google Scholar]
  49. JuanC.A. Pérez de la LastraJ.M. PlouF.J. Pérez-LebeñaE. The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies.Int. J. Mol. Sci.2021229464210.3390/ijms2209464233924958
     [Google Scholar]
  50. MurphyM.P. BayirH. BelousovV. ChangC.J. DaviesK.J.A. DaviesM.J. DickT.P. FinkelT. FormanH.J. Janssen-HeiningerY. GemsD. KaganV.E. KalyanaramanB. LarssonN.G. MilneG.L. NyströmT. PoulsenH.E. RadiR. Van RemmenH. SchumackerP.T. ThornalleyP.J. ToyokuniS. WinterbournC.C. YinH. HalliwellB. Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo.Nat. Metab.20224665166210.1038/s42255‑022‑00591‑z35760871
     [Google Scholar]
  51. RadziochD. De SanctisJ.B. WojewodkaG. RadhakrishnaM. MakriyianniI. ParentS. OuelletJ. DavidS. Lipid profile analysis in spinal trauma patients shows severe distortion of AA/DHA after injury Front.Immunol. Conf.201310.3389/conf.fimmu.2013.02.01183
     [Google Scholar]
  52. KhoubnasabjafariM. AnsarinK. JouybanA. Reliability of malondialdehyde as a biomarker of oxidative stress in psychological disorders.Bioimpacts20155312312726457249
     [Google Scholar]
  53. FujiiJ. HommaT. OsakiT. Superoxide radicals in the execution of cell death.Antioxidants202211350110.3390/antiox1103050135326151
     [Google Scholar]
  54. MaoC. YuanJ.Q. LvY.B. GaoX. YinZ.X. KrausV.B. LuoJ.S. CheiC.L. MatcharD.B. ZengY. ShiX.M. Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: A community-based cohort study.BMC Geriatr.201919110410.1186/s12877‑019‑1109‑z30987591
     [Google Scholar]
  55. LinY.W. Structure and function of heme proteins regulated by diverse post-translational modifications.Arch. Biochem. Biophys.201864113010.1016/j.abb.2018.01.00929407792
     [Google Scholar]
  56. SukumaranN.P. AmalrajA. GopiS. Neuropharmacological and cognitive effects of Bacopa monnieri (L.) Wettst – A review on its mechanistic aspects.Complement. Ther. Med.201944688210.1016/j.ctim.2019.03.01631126578
     [Google Scholar]
  57. ChaiJ. LuoL. HouF. FanX. YuJ. MaW. TangW. YangX. ZhuJ. KangW. YanJ. LiangH. Agmatine reduces lipopolysaccharide-mediated oxidant response via activating PI3K/Akt pathway and up-regulating Nrf2 and HO-1 expression in macrophages.PLoS One2016119e016363410.1371/journal.pone.016363427685463
     [Google Scholar]
  58. DejanovićB. Vuković-DejanovićV. NinkovićM. LavrnjaI. StojanovićI. PavlovićM. BegovićV. MirkovićD. StevanovićI. Effects of agmatine on chlorpromazine-induced neuronal injury in rat.Acta Vet. Brno201887214515310.2754/avb201887020145
     [Google Scholar]
  59. El-AwadyM.S. NaderM.A. SharawyM.H. The inhibition of inducible nitric oxide synthase and oxidative stress by agmatine attenuates vascular dysfunction in rat acute endotoxemic model.Environ. Toxicol. Pharmacol.201755748010.1016/j.etap.2017.08.00928837867
     [Google Scholar]
  60. BilaI. DzydzanO. BrodyakI. SybirnaN. Agmatine prevents oxidative-nitrative stress in blood leukocytes under streptozotocin-induced diabetes mellitus.Open Life Sci.201914129931010.1515/biol‑2019‑003333817163
     [Google Scholar]
  61. VaškováJ. KočanL. VaškoL. PerjésiP. Glutathione-related enzymes and proteins: A review.Molecules2023283144710.3390/molecules2803144736771108
     [Google Scholar]
  62. DejanovicB. StevanovicI. NinkovicM. StojanovicI. LavrnjaI. RadicevicT. PavlovicM. Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats.J. Vet. Sci.2016171536110.4142/jvs.2016.17.1.5327051340
     [Google Scholar]
  63. BratislavD. IrenaL. MilicaN. IvanaS. AnaD. SandaD. IvanaS. Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: The possible role of oxidant/antioxidant imbalance.Exp. Anim.2017661172710.1538/expanim.16‑001027523096
     [Google Scholar]
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Agmatine Improves Oxidative Stress Profiles in Rat Brain Tissues Induced by Sodium Azide
Curr Chem Biol 18, 129 (2024); https://doi.org/10.2174/0122127968308662240926114002
/content/journals/ccb/10.2174/0122127968308662240926114002
/content/journals/ccb/10.2174/0122127968308662240926114002
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  • Article Type:     Research Article
Keyword(s): Agmatine; antioxidative enzymes; behaviors; neurodegeneration; oxidative stress; reactive oxygen species; sodium azide

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