Skip to content
2000
image of Agmatine Improves Oxidative Stress Profiles in Rat Brain Tissues Induced by Sodium Azide

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.

Loading

Article metrics loading...

/content/journals/ccb/10.2174/0122127968308662240926114002
2024-09-14
2024-11-22
Loading full text...

Full text loading...

References

  1. Cobley J.N. Fiorello M.L. Bailey D.M. 13 reasons why the brain is susceptible to oxidative stress. Redox Biol. 2018 15 490 503 10.1016/j.redox.2018.01.008 29413961
    [Google Scholar]
  2. Sharifi-Rad M. Anil Kumar N.V. Zucca P. Varoni E.M. Dini L. Panzarini E. Rajkovic J. Tsouh Fokou P.V. Azzini E. Peluso I. Prakash Mishra A. Nigam M. El Rayess Y. Beyrouthy M.E. Polito L. Iriti M. Martins N. Martorell M. Docea A.O. Setzer W.N. Calina D. Cho W.C. Sharifi-Rad J. Lifestyle, oxidative stress, and antioxi-dants: back and forth in the pathophysiology of chronic dis-eases. Front. Physiol. 2020 11 694 10.3389/fphys.2020.00694 32714204
    [Google Scholar]
  3. Santos P. Herrmann A.P. Elisabetsky E. Piato A. Anxio-lytic properties of compounds that counteract oxidative stress, neuroinflammation, and glutamatergic dysfunction: A review. Br. J. Psychiatry 2019 41 2 168 178 10.1590/1516‑4446‑2018‑0005 30328963
    [Google Scholar]
  4. Padurariu M. Antioch I. Balmus I. Ciobica A. El-Lethey H.S. Kamel M.M. Describing some behavioural an-imal models of anxiety and their mechanistics with special reference to oxidative stress and oxytocin relevance. Int. J. Vet. Sci. Med. 2017 5 2 98 104 10.1016/j.ijvsm.2017.08.003 30255057
    [Google Scholar]
  5. About ERSH-DB 2011 Available from: https://www.cdc.gov/niosh/ershdb/about.html
  6. Zuo Y. Hu J. Xu X. Gao X. Wang Y. Zhu S. Sodium azide induces mitochondria mediated apoptosis in PC12 cells through Pgc 1α associated signaling pathway. Mol. Med. Rep. 2019 19 3 2211 2219 10.3892/mmr.2019.9853 30664159
    [Google Scholar]
  7. Van Laar V.S. Roy N. Liu A. Rajprohat S. Arnold B. Dukes A.A. Holbein C.D. Berman S.B. Glutamate exci-totoxicity in neurons triggers mitochondrial and endoplasmic reticulum accumulation of Parkin, and, in the presence of N-acetyl cysteine, mitophagy. Neurobiol. Dis. 2015 74 180 193 10.1016/j.nbd.2014.11.015 25478815
    [Google Scholar]
  8. Dukoff D.J. Hogg D.W. Hawrsyh P.J. Buck L.T. Scavenging ROS dramatically increases NMDA receptor whole cell currents in painted turtle cortical neurons. J. Exp. Biol. 2014 217 (Pt 18) jeb.105825 10.1242/jeb.105825 25063855
    [Google Scholar]
  9. Chen T. Yang Y. Luo P. Liu W. Dai S. Zheng X. Fei Z. Jiang X. Homer1 knockdown protects dopamine neurons through regulating calcium homeostasis in an in vitro model of Parkinson’s disease. Cell. Signal. 2013 25 12 2863 2870 10.1016/j.cellsig.2013.09.004 24036210
    [Google Scholar]
  10. Nöldner M. Oral treatment with the Ginkgo biloba extract EGb 761® prevents sodium azide-induced memory deficits in rats. Planta Medica Int. Open 2017 4 (S 01) S1 S202 10.1055/s‑0037‑1608413
    [Google Scholar]
  11. Ahmed M.A.E. Farouk Fahmy H. 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. 2013 36 1 39 49 10.1097/01.EHX.0000424089.76006.d7
    [Google Scholar]
  12. Olajide O.J. Akinola B.O. Ajao S.M. Enaibe B.U. Sodi-um azide-induced degenerative changes in the dorsolateral prefrontal cortex of rats: Attenuating mechanisms of kolavi-ron. Eur. J. Anat. 2016 20 1 47 64
    [Google Scholar]
  13. Delgado-Cortés M.J. Espinosa-Oliva A.M. Sarmiento M. Argüelles S. Herrera A.J. Mauriño R. Villarán R.F. Venero J.L. Machado A. de Pablos R.M. Synergistic dele-terious effect of chronic stress and sodium azide in the mouse hippocampus. Chem. Res. Toxicol. 2015 28 4 651 661 10.1021/tx5004408 25658758
    [Google Scholar]
  14. Ilesanmi O. Inala M. Ridwan A. Neuroprotective effect of ethylacetate fraction of Antiaris africana against sodium az-ide-induced neurotoxicity in the striata of male wistar rats. Iran. J. Toxicol. 2023 17 4 1 8 10.61186/IJT.17.4.1
    [Google Scholar]
  15. Molderings G.J. Haenisch B. Agmatine (decarboxylated l-arginine): Physiological role and therapeutic potential. Pharmacol. Ther. 2012 133 3 351 365 10.1016/j.pharmthera.2011.12.005 22212617
    [Google Scholar]
  16. Kotagale N. Dixit M. Garmelwar H. Bhondekar S. Ume-kar M. Taksande B. Agmatine reverses memory deficits induced by Aβ1–42 peptide in mice: A key role of imidazoline receptors. Pharmacol. Biochem. Behav. 2020 196 172976 10.1016/j.pbb.2020.172976 32598984
    [Google Scholar]
  17. Kotagale N.R. Taksande B.G. Inamdar N.N. Neuroprotec-tive offerings by agmatine. Neurotoxicology 2019 73 228 245 10.1016/j.neuro.2019.05.001 31063707
    [Google Scholar]
  18. Sirvanci-Yalabik M. Sehirli A.O. Utkan T. Aricioglu F. Agmatine, a metabolite of arginine, improves learning and memory in streptozotocin-induced Alzheimer’s disease model in rats. Klinik Psikofarmakol. BBülteni 2016 26 4 342 354 10.5455/bcp.20161121125642
    [Google Scholar]
  19. Kotagale N. Bhondekar S. Bhad M. Pise S. Charpe A. Umekar M. Taksande B. Agmatine prevents development of tolerance to anti-nociceptive effect of ethanol in mice. Alcohol 2022 101 1 8 10.1016/j.alcohol.2022.02.004 35227825
    [Google Scholar]
  20. Ostovan V.R. Amiri Z. Moezi L. Pirsalami F. Esmaili Z. Moosavi M. The effects of subchronic agmatine on pas-sive avoidance memory, anxiety-like behavior and hippo-campal Akt/GSK-3β in mice. Behav. Pharmacol. 2022 33 1 42 50 10.1097/FBP.0000000000000666 34954711
    [Google Scholar]
  21. Freitas A.E. Egea J. Buendia I. Gómez-Rangel V. Para-da E. Navarro E. Casas A.I. Wojnicz A. Ortiz J.A. Cuadrado A. Ruiz-Nuño A. Rodrigues A.L.S. Lopez M.G. Agmatine, by improving neuroplasticity markers and inducing Nrf2, prevents corticosterone-induced depressive-like behavior in mice. Mol. Neurobiol. 2016 53 5 3030 3045 10.1007/s12035‑015‑9182‑6 25966970
    [Google Scholar]
  22. El-Sayed E.K. Ahmed A.A.E. Morsy E.M.E. Nofal S. Neuroprotective effect of agmatine (decarboxylated >l -arginine) against oxidative stress and neuroinflammation in rotenone model of Parkinson’s disease. Hum. Exp. Toxicol. 2019 38 2 173 184 10.1177/0960327118788139 30001633
    [Google Scholar]
  23. Battaglia V. Grancara S. Satriano J. Saccoccio S. Agosti-nelli E. Toninello A. Agmatine prevents the Ca2+-dependent induction of permeability transition in rat brain mitochondria. Amino Acids 2010 38 2 431 437 10.1007/s00726‑009‑0402‑0 20012118
    [Google Scholar]
  24. Condello S. Currò M. Ferlazzo N. Caccamo D. Satriano J. Ientile R. Agmatine effects on mitochondrial membrane potential andNF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells. J. Neurochem. 2011 116 1 67 75 10.1111/j.1471‑4159.2010.07085.x 21044082
    [Google Scholar]
  25. Agostinelli E. Marques M.P.M. Calheiros R. Gil F.P.S.C. Tempera G. Viceconte N. Battaglia V. Grancara S. Toni-nello A. Polyamines: Fundamental characters in chemistry and biology. Amino Acids 2010 38 2 393 403 10.1007/s00726‑009‑0396‑7 20013011
    [Google Scholar]
  26. Farhan M. Rafi H. Rafiq H. Siddiqui F. Khan R. Anis J. Study of mental illness in rat model of sodium azide in-duced oxidative stress. J. Pharm. Nutr. Sci. 2019 9 4 213 221 10.29169/1927‑5951.2019.09.04.3
    [Google Scholar]
  27. Arrant A.E. Schramm-Sapyta N.L. Kuhn C.M. Use of the light/dark test for anxiety in adult and adolescent male rats. Behav. Brain Res. 2013 256 119 127 10.1016/j.bbr.2013.05.035 23721963
    [Google Scholar]
  28. Kraeuter A.K. Guest P.C. Sarnyai Z. The elevated plus maze test for measuring anxiety-like behavior in rodents. Pre-Clinical Models. Guest P. New York Humana Press 2019 69 74 10.1007/978‑1‑4939‑8994‑2_4
    [Google Scholar]
  29. Seibenhener M.L. Wooten M.C. Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J. Vis. Exp. 2015 96 96 e52434 [Journal of Visual-ized Experiments] 25742564
    [Google Scholar]
  30. Cathcart R. Schwiers E. Ames B.N. Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluo-rescein assay. Anal. Biochem. 1983 134 1 111 116 10.1016/0003‑2697(83)90270‑1 6660480
    [Google Scholar]
  31. Ohkawa H. Ohishi N. Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 1979 95 2 351 358 10.1016/0003‑2697(79)90738‑3 36810
    [Google Scholar]
  32. Kakkar P. Das B. Viswanathan P.N. A modified spectro-photometric assay of superoxide dismutase. Indian J. Biochem. Biophys. 1984 21 130 132
    [Google Scholar]
  33. Sinha A.K. Colorimetric assay of catalase. Anal. Biochem. 1972 47 2 389 394 10.1016/0003‑2697(72)90132‑7 4556490
    [Google Scholar]
  34. Ellman G.L. Tissue sulfhydryl groups. Arch. Biochem. Biophys. 1959 82 1 70 77 10.1016/0003‑9861(59)90090‑6 13650640
    [Google Scholar]
  35. Mohandas J. Marshall J.J. Duggin G.G. Horvath J.S. Tiller D.J. Differential distribution of glutathione and gluta-thione-related enzymes in rabbit kidney. Biochem. Pharmacol. 1984 33 11 1801 1807 10.1016/0006‑2952(84)90353‑8 6145422
    [Google Scholar]
  36. Winiarska-Mieczan A. Baranowska-Wójcik E. Kwiecień M. Grela E.R. Szwajgier D. Kwiatkowska K. Kiczor-owska B. The role of dietary antioxidants in the pathogene-sis of neurodegenerative diseases and their impact on cere-bral oxidoreductive balance. Nutrients 2020 12 2 435 10.3390/nu12020435 32046360
    [Google Scholar]
  37. Xu W. Gao L. Li T. Shao A. Zhang J. Neuroprotective role of agmatine in neurological diseases. Curr. Neuropharmacol. 2018 16 9 1296 1305 10.2174/1570159X15666170808120633 28786346
    [Google Scholar]
  38. van Velzen L.S. Wijdeveld M. Black C.N. van Tol M.J. van der Wee N.J.A. Veltman D.J. Penninx B.W.J.H. Schmaal L. Oxidative stress and brain morphology in indi-viduals with depression, anxiety and healthy controls. Prog. Neuropsychopharmacol. Biol. Psychiatry 2017 76 140 144 10.1016/j.pnpbp.2017.02.017 28249819
    [Google Scholar]
  39. Black C.N. Bot M. Scheffer P.G. Penninx B.W.J.H. Oxi-dative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort. Psychol. Med. 2017 47 5 936 948 10.1017/S0033291716002828 27928978
    [Google Scholar]
  40. Miller M.W. Lin A.P. Wolf E.J. Miller D.R. Oxidative stress, inflammation, and neuroprogression in chronic PTSD. Harv. Rev. Psychiatry 2018 26 2 57 69 10.1097/HRP.0000000000000167 29016379
    [Google Scholar]
  41. Bhatt S. Nagappa A.N. Patil C.R. Role of oxidative stress in depression. Drug Discov. Today 2020 25 7 1270 1276 10.1016/j.drudis.2020.05.001 32404275
    [Google Scholar]
  42. Correia A.S. Cardoso A. Vale N. Oxidative stress in de-pression: The link with the stress response, neuroinflamma-tion, serotonin, neurogenesis and synaptic plasticity. Antioxidants 2023 12 2 470 10.3390/antiox12020470 36830028
    [Google Scholar]
  43. Filipović D. Todorović N. Bernardi R.E. Gass P. Oxida-tive and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxie-ty-like symptoms. Brain Struct. Funct. 2017 222 1 1 20 10.1007/s00429‑016‑1218‑9 27033097
    [Google Scholar]
  44. Atrooz F. Alkadhi K.A. Salim S. Understanding stress: Insights from rodent models. Curr. Res. Neurobiol. 2021 2 100013 10.1016/j.crneur.2021.100013 36246514
    [Google Scholar]
  45. Rafi H. Rafiq H. Farhan M. Inhibition of NMDA receptors by agmatine is followed by GABA/glutamate balance in ben-zodiazepine withdrawal syndrome. Beni. Suef Univ. J. Basic Appl. Sci. 2021 10 1 13
    [Google Scholar]
  46. Jin H. Kanthasamy A. Ghosh A. Anantharam V. Kal-yanaraman B. Kanthasamy A.G. Mitochondria-targeted an-tioxidants for treatment of Parkinson’s disease: Preclinical and clinical outcomes. Biochim. Biophys. Acta Mol. Basis Dis. 2014 1842 8 1282 1294 10.1016/j.bbadis.2013.09.007 24060637
    [Google Scholar]
  47. Singh A. Kukreti R. Saso L. Kukreti S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules 2019 24 8 1583 10.3390/molecules24081583 31013638
    [Google Scholar]
  48. Collin F. Chemical basis of reactive oxygen species reactivi-ty and involvement in neurodegenerative diseases. Int. J. Mol. Sci. 2019 20 10 2407 10.3390/ijms20102407 31096608
    [Google Scholar]
  49. Juan C.A. Pérez de la Lastra J.M. Plou F.J. Pérez-Lebeña E. The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, li-pids and proteins) and induced pathologies. Int. J. Mol. Sci. 2021 22 9 4642 10.3390/ijms22094642 33924958
    [Google Scholar]
  50. Murphy M.P. Bayir H. Belousov V. Chang C.J. Davies K.J.A. Davies M.J. Dick T.P. Finkel T. Forman H.J. Janssen-Heininger Y. Gems D. Kagan V.E. Kalyana-raman B. Larsson N.G. Milne G.L. Nyström T. Poulsen H.E. Radi R. Van Remmen H. Schumacker P.T. Thornal-ley P.J. Toyokuni S. Winterbourn C.C. Yin H. Halliwell B. Guidelines for measuring reactive oxygen species and ox-idative damage in cells and in vivo. Nat. Metab. 2022 4 6 651 662 10.1038/s42255‑022‑00591‑z 35760871
    [Google Scholar]
  51. Radzioch D. De Sanctis J.B. Wojewodka G. Radhakrish-na M. Makriyianni I. Parent S. Ouellet J. David S. Lipid profile analysis in spinal trauma patients shows severe dis-tortion of AA/DHA after injury Front. Immunol. Conf. 2013 10.3389/conf.fimmu.2013.02.01183
    [Google Scholar]
  52. Khoubnasabjafari M. Ansarin K. Jouyban A. Reliability of malondialdehyde as a biomarker of oxidative stress in psychological disorders. Bioimpacts 2015 5 3 123 127 26457249
    [Google Scholar]
  53. Fujii J. Homma T. Osaki T. Superoxide radicals in the execution of cell death. Antioxidants 2022 11 3 501 10.3390/antiox11030501 35326151
    [Google Scholar]
  54. Mao C. Yuan J.Q. Lv Y.B. Gao X. Yin Z.X. Kraus V.B. Luo J.S. Chei C.L. Matchar D.B. Zeng Y. Shi X.M. Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: A community-based cohort study. BMC Geriatr. 2019 19 1 104 10.1186/s12877‑019‑1109‑z 30987591
    [Google Scholar]
  55. Lin Y.W. Structure and function of heme proteins regulated by diverse post-translational modifications. Arch. Biochem. Biophys. 2018 641 1 30 10.1016/j.abb.2018.01.009 29407792
    [Google Scholar]
  56. Sukumaran N.P. Amalraj A. Gopi S. Neuropharmacologi-cal and cognitive effects of Bacopa monnieri (L.) Wettst – A review on its mechanistic aspects. Complement. Ther. Med. 2019 44 68 82 10.1016/j.ctim.2019.03.016 31126578
    [Google Scholar]
  57. Chai J. Luo L. Hou F. Fan X. Yu J. Ma W. Tang W. Yang X. Zhu J. Kang W. Yan J. Liang H. Agmatine re-duces lipopolysaccharide-mediated oxidant response via ac-tivating PI3K/Akt pathway and up-regulating Nrf2 and HO-1 expression in macrophages. PLoS One 2016 11 9 e0163634 10.1371/journal.pone.0163634 27685463
    [Google Scholar]
  58. Dejanović B. Vuković-Dejanović V. Ninković M. Lavrn-ja I. Stojanović I. Pavlović M. Begović V. Mirković D. Stevanović I. Effects of agmatine on chlorpromazine-induced neuronal injury in rat. Acta Vet. Brno 2018 87 2 145 153 10.2754/avb201887020145
    [Google Scholar]
  59. El-Awady M.S. Nader M.A. Sharawy M.H. The inhibition of inducible nitric oxide synthase and oxidative stress by agmatine attenuates vascular dysfunction in rat acute endo-toxemic model. Environ. Toxicol. Pharmacol. 2017 55 74 80 10.1016/j.etap.2017.08.009 28837867
    [Google Scholar]
  60. Bila I. Dzydzan O. Brodyak I. Sybirna N. Agmatine prevents oxidative-nitrative stress in blood leukocytes under streptozotocin-induced diabetes mellitus. Open Life Sci. 2019 14 1 299 310 10.1515/biol‑2019‑0033 33817163
    [Google Scholar]
  61. Vašková J. Kočan L. Vaško L. Perjési P. Glutathione-related enzymes and proteins: A review. Molecules 2023 28 3 1447 10.3390/molecules28031447 36771108
    [Google Scholar]
  62. Dejanovic B. Stevanovic I. Ninkovic M. Stojanovic I. Lavrnja I. Radicevic T. Pavlovic M. Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats. J. Vet. Sci. 2016 17 1 53 61 10.4142/jvs.2016.17.1.53 27051340
    [Google Scholar]
  63. Bratislav D. Irena L. Milica N. Ivana S. Ana D. Sanda D. Ivana S. Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: The possible role of oxi-dant/antioxidant imbalance. Exp. Anim. 2017 66 1 17 27 10.1538/expanim.16‑0010 27523096
    [Google Scholar]
/content/journals/ccb/10.2174/0122127968308662240926114002
Loading
/content/journals/ccb/10.2174/0122127968308662240926114002
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: reactive oxygen species ; Agmatine ; sodium azide ; oxidative stress ; antioxidative enzymes
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test