Evaluation of the antioxidant effect of olanzapine in combination with N Acetyl Cysteine in a mouse model of schizophrenia induced by MK-801.

Authors

  • Reyna Lamas-Aguilar Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez. Mexico City, Mexico.
  • Iván Pérez-Neri Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez. Mexico City, Mexico. https://orcid.org/0000-0003-0190-7272
  • Camilo Rios Molecular Neuropharmacology Laboratory, Department of Biological Systems, Universidad Autónoma Metropolitana, Xochimilco Unit. Mexico City, Mexico. https://orcid.org/0000-0001-5407-1558
  • Alfonso Mata-Bermúdez Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez. Mexico City, Mexico https://orcid.org/0000-0002-2234-7019
  • Erick Martínez Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez. Mexico City, Mexico
  • Norman Manning Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez. Mexico City, Mexico
  • Araceli Diaz-Ruiz Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez. Mexico City, Mexico https://orcid.org/0000-0002-1481-0966

DOI:

https://doi.org/10.31157/an.v28i3.399

Keywords:

Modelo de esquizofrenia; MK-801; Olanzapina, N-acetil Cisteína; Lipoperoxidación; Glutatión Reducido.

Abstract

Introduction: Schizophrenia is a chronic condition that affects 1% of the population. One of the main theories that explain the etiology of schizophrenia is related to the hypofunction of glutamate N-Methyl-d-Aspartate (NMDA) receptors, inducing the loss of balance between the production of oxidant species produced in the metabolism. cell and antioxidant defense systems, which generates a state of oxidative stress. N-acetylcysteine (NAC) has been proposed as an adjuvant agent to enhance the effectiveness of atypical antipsychotics such as olanzapine, improving the oxidation processes inherent to the disease. Methods: 30 mice divided into 5 experimental groups were used and MK-801 (an NMDA antagonist) was administered as a model of schizophrenia. The participation of oxidative stress was evaluated by measuring lipid peroxidation and reduced glutathione concentration at the level of the frontal cortex. Results: The administration of MK-801 produced an increase in lipid peroxidation and a decrease in the concentration of reduced glutathione at the level of the frontal cortex. In this same sense, both treatment with Olanzapine (OLA) and with NAC and with the combination of OLA-NAC decreased lipid peroxidation and increased glutathione in brain tissue. Discussion: These data suggest that treatment with OLA and NAC could regulate the oxidative damage inherent to the disease and represent a therapeutic option for patients with chronic psychosis or even those resistant to pharmacological treatment.

References

Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, et al. Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophr Bull. 17 de octubre de 2018;44(6):1195-203. doi: 10.1093/schbul/sby058. DOI: https://doi.org/10.1093/schbul/sby058

McCutcheon RA, Marques TR, Howes OD. Schizophrenia—An Overview. JAMA Psychiatry. 1 de febrero de 2020;77(2):201-10. doi: 10.1001/jamapsychiatry.2019.3360. DOI: https://doi.org/10.1001/jamapsychiatry.2019.3360

Laursen TM, Nordentoft M, Mortensen PB. Excess Early Mortality in Schizophrenia. Annu Rev Clin Psychol. 28 de marzo de 2014;10(1):425-48. doi: 10.1146/annurev-clinpsy-032813-153657. DOI: https://doi.org/10.1146/annurev-clinpsy-032813-153657

Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis - The Lancet Psychiatry [Internet]. [citado 6 de abril de 2020]. Disponible en: https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(17)30078-0/fulltext

Charlson FJ, Baxter AJ, Dua T, Degenhardt L, Whiteford HA, Vos T. Excess mortality from mental, neurological and substance use disorders in the Global Burden of Disease Study 2010. Epidemiol Psychiatr Sci. abril de 2015;24(2):121-40. doi: 10.1596/978-1-4648-0426-7_ch3 DOI: https://doi.org/10.1017/S2045796014000687

Aquino-Miranda G, Rivera-Ramírez N, Márquez-Gómez R, Escamilla-Sánchez J, González-Pantoja R, Ramos-Languren L-E, et al. Histamine H3 receptor activation reduces the impairment in prepulse inhibition (PPI) of the acoustic startle response and Akt phosphorylation induced by MK-801 (dizocilpine), antagonist at N-Methyl-d-Aspartate (NMDA) receptors. Prog Neuropsychopharmacol Biol Psychiatry. 30 de 2019;94:109653. doi: 10.1016/j.pnpbp.2019.109653. Epub 2019 May 17. DOI: https://doi.org/10.1016/j.pnpbp.2019.109653

Nakazawa K, Sapkota K. The origin of NMDA receptor hypofunction in schizophrenia. Pharmacol Ther. 2020;205:107426. doi: 10.1016/j.pharmthera.2019.107426. DOI: https://doi.org/10.1016/j.pharmthera.2019.107426

Slifstein M, van de Giessen E, Van Snellenberg J, Thompson JL, Narendran R, Gil R, et al. Deficits in prefrontal cortical and extrastriatal dopamine release in schizophrenia: a positron emission tomographic functional magnetic resonance imaging study. JAMA Psychiatry. abril de 2015;72(4):316-24. doi: 10.1001/jamapsychiatry.2014.2414. DOI: https://doi.org/10.1001/jamapsychiatry.2014.2414

Miller EK, Cohen JD. An integrative theory of prefrontal cortex function. Annu Rev Neurosci. 2001;24:167-202. doi: 10.1146/annurev.neuro.24.1.167. DOI: https://doi.org/10.1146/annurev.neuro.24.1.167

Hoffman P. The meaning of ‘life’ and other abstract words: Insights from neuropsychology. J Neuropsychol. 2016;10(2):317-43. doi: 10.1111/jnp.12065. Epub 2015 Feb 23. DOI: https://doi.org/10.1111/jnp.12065

Wood SJ, Yücel M, Pantelis C, Berk M. Neurobiology of Schizophrenia Spectrum Disorders: The Role of Oxidative Stress. 2009;38(5):6. DOI: https://doi.org/10.47102/annals-acadmedsg.V38N5p396

Robertson OD, Coronado NG, Sethi R, Berk M, Dodd S. Putative neuroprotective pharmacotherapies to target the staged progression of mental illness. Early Interv Psychiatry. 2019;13(5):1032-49. doi: 10.1111/eip.12775. DOI: https://doi.org/10.1111/eip.12775

Moylan S, Berk M, Dean OM, Samuni Y, Williams LJ, O’Neil A, et al. Oxidative & nitrosative stress in depression: Why so much stress? Neurosci Biobehav Rev. 1 de septiembre de 2014;45:46-62. doi: 10.1016/j.neubiorev.2014.05.007. DOI: https://doi.org/10.1016/j.neubiorev.2014.05.007

Halliwell B. Role of Free Radicals in the Neurodegenerative Diseases. Drugs Aging. 1 de septiembre de 2001;18(9):685-716. doi: 10.2165/00002512-200118090-00004. DOI: https://doi.org/10.2165/00002512-200118090-00004

Bavarsad Shahripour R, Harrigan MR, Alexandrov AV. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav. marzo de 2014;4(2):108-22. doi: 10.1002/brb3.208. Epub 2014 Jan 13. DOI: https://doi.org/10.1002/brb3.208

Andreazza AC, Frey BN, Valvassori SS, Zanotto C, Gomes KM, Comim CM, et al. DNA damage in rats after treatment with methylphenidate. Prog Neuropsychopharmacol Biol Psychiatry. 15 de agosto de 2007;31(6):1282-8. doi: 10.1016/j.pnpbp.2007.05.012. DOI: https://doi.org/10.1016/j.pnpbp.2007.05.012

Su L-J, Zhang J-H, Gomez H, Murugan R, Hong X, Xu D, et al. Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis. Oxid Med Cell Longev. 13 de octubre de 2019;2019:e5080843. doi: 10.1155/2019/5080843. DOI: https://doi.org/10.1155/2019/5080843

Que X, Hung M-Y, Yeang C, Gonen A, Prohaska TA, Sun X, et al. Oxidized Phospholipids are Proinflammatory and Proatherogenic in Hypercholesterolemic Mice. Nature. junio de 2018;558(7709):301-6. doi: 10.1038/s41586-018-0198-8 DOI: https://doi.org/10.1038/s41586-018-0198-8

Berk M, Ng F, Dean O, Dodd S, Bush AI. Glutathione: a novel treatment target in psychiatry. Trends Pharmacol Sci. 1 de julio de 2008;29(7):346-51. doi: 10.1016/j.tips.2008.05.001. DOI: https://doi.org/10.1016/j.tips.2008.05.001

Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science. 30 de abril de 1976;192(4238):481-3. doi: 10.1126/science.3854. DOI: https://doi.org/10.1126/science.3854

Kaar SJ, Natesan S, McCutcheon R, Howes OD. Antipsychotics: Mechanisms underlying clinical response and side-effects and novel treatment approaches based on pathophysiology. Neuropharmacology. 1 de agosto de 2020;172:107704. doi: 10.1016/j.neuropharm.2019.107704. DOI: https://doi.org/10.1016/j.neuropharm.2019.107704

Vaquero-Baez M, Díaz-Ruíz A, Tristán-López L, Aviña-Cervantes C, Torner C, Ramírez-Bermúdez J, et al. Clozapine and desmethylclozapine: correlation with neutrophils and leucocytes counting in Mexican patients with schizophrenia. BMC Psychiatry. 9 de octubre de 2019;19(1):295. doi: 10.1186/s12888-019-2286-1. DOI: https://doi.org/10.1186/s12888-019-2286-1

Lowe P, Krivoy A, Porffy L, Henriksdottir E, Eromona W, Shergill SS. When the drugs don’t work: treatment-resistant schizophrenia, serotonin and serendipity. Ther Adv Psychopharmacol. 1 de enero de 2018;8(1):63-70. doi: 10.1177/2045125317737003. DOI: https://doi.org/10.1177/2045125317737003

Komossa K, Rummel‐Kluge C, Hunger H, Schmid F, Schwarz S, Duggan L, et al. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev [Internet]. 2010 [citado 13 de mayo de 2020];(3). Disponible en: https://www-cochranelibrary-com.pbidi.unam.mx:2443/cdsr/doi/10.1002/14651858.CD006654.pub2/full DOI: https://doi.org/10.1002/14651858.CD006654.pub2

Fulton B, Goa KL. Olanzapine: A Review of its Pharmacological Properties and Therapeutic Efficacy in the Management of Schizophrenia and Related Psychoses. Drugs. febrero de 1997;53(2):281-98. doi: 10.2165/00003495-199753020-00007. DOI: https://doi.org/10.2165/00003495-199753020-00007

Wang H, Xu H, Dyck LE, Li X-M. Olanzapine and quetiapine protect PC12 cells from β-amyloid peptide25–35-induced oxidative stress and the ensuing apoptosis. J Neurosci Res. 2005;81(4):572-80. doi: 10.1002/jnr.20570. DOI: https://doi.org/10.1002/jnr.20570

Barbosa L, Bernardo M. Utilización de olanzapina en el tratamiento de la esquizofrenia y el trastorno bipolar. Psiquiatr Biológica. enero de 2016;23(1):4-22. DOI: https://doi.org/10.1016/j.psiq.2015.10.008

Atmaca M, Kuloglu M, Ustundag B. Serum Leptin and Triglyceride Levels in Patients on Treatment With Atypical Antipsychotics. J Clin Psychiatry. 15 de mayo de 2003;64(5):598-604. doi: 10.4088/jcp.v64n0516. DOI: https://doi.org/10.4088/JCP.v64n0516

Abdul-Monim Z, Reynolds GP, Neill JC. The effect of atypical and classical antipsychotics on sub-chronic PCP-induced cognitive deficits in a reversal-learning paradigm. Behav Brain Res. mayo de 2006;169(2):263-73 doi: 10.1016/j.bbr.2006.01.019. DOI: https://doi.org/10.1016/j.bbr.2006.01.019

Goetghebeur P, Dias R. Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set-shifting impairment following subchronic PCP administration in the rat—a back translational study. Psychopharmacology (Berl). enero de 2009;202(1-3):287-93. doi: 10.1007/s00213-008-1132-9. DOI: https://doi.org/10.1007/s00213-008-1132-9

Song JC, Seo MK, Park SW, Lee JG, Kim YH. Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice. Clin Psychopharmacol Neurosci. 31 de agosto de 2016;14(3):279-85. doi: 10.9758/cpn.2016.14.3.279. DOI: https://doi.org/10.9758/cpn.2016.14.3.279

Liu X, Li J, Guo C, Wang H, Sun Y, Wang H, et al. Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits. Front Behav Neurosci [Internet]. 2018 [citado 13 de mayo de 2020];11. Disponible en: https://www.frontiersin.org/articles/10.3389/fnbeh.2017.00260/full DOI: https://doi.org/10.3389/fnbeh.2017.00260

Park SW, Lee CH, Cho HY, Seo MK, Lee JG, Lee BJ, et al. Effects of antipsychotic drugs on the expression of synaptic proteins and dendritic outgrowth in hippocampal neuronal cultures. Synap N Y N. mayo de 2013;67(5):224-34. doi: 10.1002/syn.21634. DOI: https://doi.org/10.1002/syn.21634

Reddy NR, Krishnamurthy S. Repeated olanzapine treatment mitigates PTSD like symptoms in rats with changes in cell signaling factors. Brain Res Bull. 1 de junio de 2018;140:365-77. doi: 10.1016/j.brainresbull.2018.06.003. DOI: https://doi.org/10.1016/j.brainresbull.2018.06.003

Boz, Z., Hu, M., Yu, Y., & Huang, X. (5 de Nov de 2020). N-acetylcysteine prevents olanzapine-induced oxidative stress in mHypoA-59 hypothalamic neurons. Scientific Reports. doi:10.1038/s41598-020-75356-3. doi: 10.1038/s41598-020-75356-3. DOI: https://doi.org/10.1038/s41598-020-75356-3

Scalley RD, Conner CS. Acetaminophen poisoning: a case report of the use of acetylcysteine. Am J Hosp Pharm. agosto de 1978;35(8):964-7. DOI: https://doi.org/10.1093/ajhp/35.8.964

Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther. 1 de diciembre de 2008;8(12):1955-62. doi: 10.1517/14728220802517901. DOI: https://doi.org/10.1517/14728220802517901

Rossell SL, Francis PS, Galletly C, Harris A, Siskind D, Berk M, et al. N -acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double-blind randomised placebo controlled trial targeting negative symptoms. BMC Psychiatry. diciembre de 2016;16(1):1-9. doi: 10.1186/s12888-016-1030-3. DOI: https://doi.org/10.1186/s12888-016-1030-3

Deepmala, Slattery J, Kumar N, Delhey L, Berk M, Dean O, et al. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neurosci Biobehav Rev. 1 de agosto de 2015;55:294-321. doi: 10.1016/j.neubiorev.2015.04.015. DOI: https://doi.org/10.1016/j.neubiorev.2015.04.015

Kerksick C, Willoughby D. The Antioxidant Role of Glutathione and N-Acetyl-Cysteine Supplements and Exercise-Induced Oxidative Stress. J Int Soc Sports Nutr. 1 de diciembre de 2005;2(2):38. doi: 10.1186/1550-2783-2-2-38. DOI: https://doi.org/10.1186/1550-2783-2-2-38

Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 1 de marzo de 2011;36(2):78-86. doi: 10.1503/jpn.100057. DOI: https://doi.org/10.1503/jpn.100057

Quintavalle C, Donnarumma E, Fiore D, Briguori C, Condorelli G. Therapeutic strategies to prevent contrast-induced acute kidney injury. Curr Opin Cardiol. noviembre de 2013;28(6):676-82. doi: 10.1097/HCO.0b013e3283653f41. DOI: https://doi.org/10.1097/HCO.0b013e3283653f41

Smaga I, Pomierny B, Krzyżanowska W, Pomierny-Chamioło L, Miszkiel J, Niedzielska E, et al. N-acetylcysteine possesses antidepressant-like activity through reduction of oxidative stress: Behavioral and biochemical analyses in rats. Prog Neuropsychopharmacol Biol Psychiatry. 3 de diciembre de 2012;39(2):280-7. doi: 10.1016/j.pnpbp.2012.06.018. DOI: https://doi.org/10.1016/j.pnpbp.2012.06.018

Diaz-Ruiz A, Alcaraz-Zubeldia M, Maldonado V, Salgado-Ceballos H, Mendez-Armenta M, Rios C. Differential time-course of the increase of antioxidant thiol-defenses in the acute phase after spinal cord injury in rats. Neurosci Lett. 2009 Mar 6;452(1):56-9. doi: 10.1016/j.neulet.2009.01.020. DOI: https://doi.org/10.1016/j.neulet.2009.01.020

Triggs WJ, Willmore LJ. In vivo lipid peroxidation in rat brain following intracortical Fe2+ injection. J Neurochem. 1984 Apr;42(4):976-80. doi: 10.1111/j.1471-4159.1984.tb12699.x. DOI: https://doi.org/10.1111/j.1471-4159.1984.tb12699.x

Diaz-Ruiz, A., Rios, C., Duarte, I., Correa, D., Guizar-Sahagun, G., Grijalva, I., Ibarra, A. (1999). Cyclosporin-A inhibits lipid peroxidation after spinal cord injury in rats. Neurosci Lett 266, 61–64). doi: 10.1016/s0304-3940(99)00255-4. DOI: https://doi.org/10.1016/S0304-3940(99)00255-4

Nucifora LG, Tanaka T, Hayes LN, Kim M, Lee BJ, Matsuda T, et al. Reduction of plasma glutathione in psychosis associated with schizophrenia and bipolar disorder in translational psychiatry. Transl Psychiatry. agosto de 2017;7(8):e1215. doi: 10.1038/tp.2017.178. DOI: https://doi.org/10.1038/tp.2017.178

Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, et al. N-Acetyl Cysteine as a Glutathione Precursor for Schizophrenia—A Double-Blind, Randomized, Placebo-Controlled Trial. Biol Psychiatry. 1 de septiembre de 2008;64(5):361-8. doi: 10.1016/j.biopsych.2008.03.004. DOI: https://doi.org/10.1016/j.biopsych.2008.03.004

Do KQ, Trabesinger AH, Kirsten‐Krüger M, Lauer CJ, Dydak U, Hell D, et al. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci. 2000;12(10):3721-8. doi: 10.1046/j.1460-9568.2000.00229.x. DOI: https://doi.org/10.1046/j.1460-9568.2000.00229.x

Farokhnia M, Azarkolah A, Adinehfar F, Khodaie-Ardakani M-R, Hosseini S-M-R, Yekehtaz H, et al. N-Acetylcysteine as an Adjunct to Risperidone for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study. Clin Neuropharmacol. diciembre de 2013;36(6):185–192. doi: 10.1097/WNF.0000000000000001. DOI: https://doi.org/10.1097/WNF.0000000000000001

Sepehrmanesh Z, Heidary M, Akasheh N, Akbari H, Heidary M. Therapeutic effect of adjunctive N-acetyl cysteine (NAC) on symptoms of chronic schizophrenia: A double-blind, randomized clinical trial. Prog Neuropsychopharmacol Biol Psychiatry. 02 de 2018;82:289-96. doi: 10.1016/j.pnpbp.2017.11.001. DOI: https://doi.org/10.1016/j.pnpbp.2017.11.001

Dean OM, Mancuso SG, Bush AI, Copolov D, Do KQ, Cuénod M, et al. Benefits of adjunctive N-acetylcysteine in a sub-group of clozapine-treated individuals diagnosed with schizophrenia. Psychiatry Res. 30 de diciembre de 2015;230(3):982-3 doi: 10.1016/j.psychres.2015.10.037. DOI: https://doi.org/10.1016/j.psychres.2015.10.037

Downloads

Additional Files

Published

2022-11-24

How to Cite

Lamas-Aguilar, R., Pérez-Neri, I., Rios, C., Mata-Bermúdez, A., Martínez, E., Manning, N., & Diaz-Ruiz, A. (2022). Evaluation of the antioxidant effect of olanzapine in combination with N Acetyl Cysteine in a mouse model of schizophrenia induced by MK-801. Archivos De Neurociencias, 28(3). https://doi.org/10.31157/an.v28i3.399

Issue

Vol. 28 No. 3 (2023)

Section

Original Articles

License

Copyright (c) 2023 Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

September 2022-present © Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez. Open access articles under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. No commercial re-use is allowed.

January-September 2022 © The authors. Open access articles under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. No commercial re-use is allowed.

January 2014-December 2021 © Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez. Open access articles under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Most read articles by the same author(s)

1 2 3 4 > >>