OpenLB
Open Library of Bioscience
Advanced Search
Molecules (Basel, Switzerland)
Sep 14, 2020;25 (18):

Atypical Antipsychotic Drug Ziprasidone Protects against Rotenone-Induced Neurotoxicity: An In Vitro Study.

Kazuki Terada, Ayumi Murata, Erina Toki, Shotaro Goto, Hirofumi Yamakawa, Shuichi Setoguchi, Daisuke Watase, Mitsuhisa Koga, Jiro Takata, Kazuhisa Matsunaga, Yoshiharu Karube
Author Information
  1. Kazuki Terada: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  2. Ayumi Murata: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  3. Erina Toki: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  4. Shotaro Goto: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  5. Hirofumi Yamakawa: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  6. Shuichi Setoguchi: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  7. Daisuke Watase: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  8. Mitsuhisa Koga: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  9. Jiro Takata: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  10. Kazuhisa Matsunaga: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
  11. Yoshiharu Karube: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
PMID: 32937854 DOI: 10.3390/molecules25184206

Abstract

Schizophrenia is a severe, chronic mental illness characterized by delusions, hallucinations, negative symptoms, and cognitive dysfunction. Recently, several studies have demonstrated that the pathogenesis of Schizophrenia involves mitochondrial dysfunction and oxidative stress. However, the effect of antipsychotic drugs for these events has been poorly investigated. In the present study, we evaluated the neuroprotective effect of an atypical antipsychotic drug, ziprasidone (ZPD), on Rotenone (ROT)-induced Neurotoxicity involving oxidative stress in PC12 cells. Our data showed that ZPD treatment promoted the translocation of NF-E2-related factor-2 (Nrf2) from cytoplasm to nucleus and activated the expression of its target genes NAD(P)H quinone oxidoreductase (NQO-1), catalase (CAT), and heme oxygenase (HO-1). Additionally, ZPD prevented ROT-induced cell death and intracellular reactive oxygen species production. Interestingly, the use of serotonin 5-HT receptor antagonist 1-(2-methoxyphenyl)-4 (4-(2-phtalimido) butyl) piperazine (NAN-190) completely blocked the protective effect of ZPD against ROT-induced cell death. Our results demonstrate the neuroprotective effect of ZPD against ROT-induced Neurotoxicity and suggest that ZPD may be a potential candidate for the prevention of mitochondrial dysfunction and oxidative stress in Schizophrenia.

Keywords

Nrf2 pathway antioxidant enzyme mitochondrial dysfunction neurotoxicity oxidative stress rotenone schizophrenia ziprasidone

References

  1. Psychiatry Clin Neurosci. 2005 Dec;59(6):652-6 [PMID: 16401239]
  2. Eur J Pharmacol. 2002 Apr 26;441(3):137-40 [PMID: 12063084]
  3. Mol Psychiatry. 2005 Jan;10(1):27-39 [PMID: 15340352]
  4. Biomed Pharmacother. 2016 Jul;81:411-415 [PMID: 27261620]
  5. Basic Clin Pharmacol Toxicol. 2007 Nov;101(5):315-9 [PMID: 17910614]
  6. Clin Psychopharmacol Neurosci. 2015 Apr 30;13(1):62-7 [PMID: 25912539]
  7. Brain Res. 2007 May 4;1144:192-201 [PMID: 17336276]
  8. J Neurosci Res. 2009 May 15;87(7):1659-69 [PMID: 19125416]
  9. Sci China Life Sci. 2010 Jan;53(1):112-124 [PMID: 20596963]
  10. Psychopharmacology (Berl). 2005 Nov;182(4):494-8 [PMID: 16133138]
  11. Brain Res. 2008 Mar 14;1199:159-66 [PMID: 18269931]
  12. J Neurochem. 2007 Oct;103(1):303-11 [PMID: 17587308]
  13. Arch Gen Psychiatry. 2007 Jan;64(1):19-28 [PMID: 17199051]
  14. Pharmacol Biochem Behav. 2004 Aug;78(4):751-6 [PMID: 15301931]
  15. Biol Psychiatry. 2013 Sep 15;74(6):400-9 [PMID: 23683390]
  16. Muscle Nerve. 1994 Jun;17(6):614-22 [PMID: 8196704]
  17. Mol Psychiatry. 2004 Jul;9(7):684-97, 643 [PMID: 15098003]
  18. Neuropharmacology. 2001 Jun;40(7):899-910 [PMID: 11378160]
  19. PLoS One. 2018 Dec 17;13(12):e0209250 [PMID: 30557385]
  20. Free Radic Biol Med. 2008 Nov 15;45(10):1375-83 [PMID: 18824091]
  21. Redox Biol. 2018 Apr;14:609-617 [PMID: 29154192]
  22. Biol Psychiatry. 2014 Jun 15;75(12):936-44 [PMID: 24331955]
  23. Sci Rep. 2016 Aug 24;6:32206 [PMID: 27553905]
  24. Neurosci Res. 2011 Apr;69(4):283-90 [PMID: 21238512]
  25. Antioxid Redox Signal. 2018 Dec 10;29(17):1727-1745 [PMID: 28899199]
  26. Redox Biol. 2015;4:87-96 [PMID: 25529839]
  27. CMAJ. 2005 Jun 21;172(13):1703-11 [PMID: 15967975]
  28. J Neuropathol Exp Neurol. 2007 Jan;66(1):75-85 [PMID: 17204939]
  29. Sci Rep. 2018 Jan 8;8(1):26 [PMID: 29311595]
  30. J Biol Chem. 2003 Mar 7;278(10):8516-25 [PMID: 12496265]
  31. Psychiatry Clin Neurosci. 2018 May;72(5):329-336 [PMID: 29280533]
  32. Schizophr Res. 2001 Mar 1;48(1):125-36 [PMID: 11278159]
  33. Free Radic Res. 2013 May;47(5):357-67 [PMID: 23472882]
  34. Acta Pharmacol Toxicol (Copenh). 1963;20:140-4 [PMID: 14060771]
  35. Toxicol Pathol. 2002 Nov-Dec;30(6):620-50 [PMID: 12512863]
  36. Neurochem Res. 1993 Apr;18(4):479-83 [PMID: 7682661]
  37. Biol Psychiatry. 2008 Sep 1;64(5):361-8 [PMID: 18436195]
  38. Eur J Pharmacol. 2001 Aug 17;425(3):197-201 [PMID: 11513838]
  39. Schizophr Res. 2003 Aug 1;62(3):213-24 [PMID: 12837517]
  40. Front Neurosci. 2019 Feb 04;13:30 [PMID: 30778282]
  41. Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7673-5 [PMID: 10884398]
  42. J Biol Chem. 2015 Nov 6;290(45):27425-37 [PMID: 26416893]
  43. J Cereb Blood Flow Metab. 2005 Apr;25(4):451-9 [PMID: 15674237]
  44. Invest Ophthalmol Vis Sci. 2011 Apr 04;52(5):2118-26 [PMID: 21087971]

MeSH Term

Animals
Antioxidants
Antipsychotic Agents
Apoptosis
Cell Death
Cell Nucleus
Cell Survival
Cytoplasm
Mice
Mitochondrial Diseases
NF-E2-Related Factor 2
Nerve Growth Factor
Neuroprotective Agents
Oxidative Stress
PC12 Cells
Piperazines
Rats
Reactive Oxygen Species
Receptor, Serotonin, 5-HT1A
Rotenone
Thiazoles

Chemicals

Antioxidants
Antipsychotic Agents
NF-E2-Related Factor 2
Neuroprotective Agents
Nfe2l2 protein, rat
Piperazines
Reactive Oxygen Species
Thiazoles
Rotenone
Receptor, Serotonin, 5-HT1A
ziprasidone
Nerve Growth Factor
Journal Article
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0ZPDdysfunctionoxidativestresseffectschizophreniamitochondrialneurotoxicityROT-inducedantipsychoticneuroprotectiveziprasidonerotenoneNrf2celldeathSchizophreniaseverechronicmentalillnesscharacterizeddelusionshallucinationsnegativesymptomscognitiveRecentlyseveralstudiesdemonstratedpathogenesisinvolvesHoweverdrugseventspoorlyinvestigatedpresentstudyevaluatedatypicaldrugROT-inducedinvolvingPC12cellsdatashowedtreatmentpromotedtranslocationNF-E2-relatedfactor-2cytoplasmnucleusactivatedexpressiontargetgenesNADPHquinoneoxidoreductaseNQO-1catalaseCAThemeoxygenaseHO-1AdditionallypreventedintracellularreactiveoxygenspeciesproductionInterestinglyuseserotonin5-HTreceptorantagonist1-2-methoxyphenyl-44-2-phtalimidobutylpiperazineNAN-190completelyblockedprotectiveresultsdemonstratesuggestmaypotentialcandidatepreventionAtypicalAntipsychoticDrugZiprasidoneProtectsRotenone-InducedNeurotoxicity:VitroStudypathwayantioxidantenzyme

Similar Articles

Cited By (5)