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Protective Effect of Nerolidol Against Pentylenetetrazol-Induced Kindling, Oxidative Stress and Associated Behavioral Comorbidities in Mice

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Abstract

The present study was aimed to investigate the effect of nerolidol on the development of kindling and associate oxidative stress and behavioral comorbidities. Kindling was induced by repeated injections of a sub-convulsive dose of pentylenetetrazol (PTZ-35 mg/kg; i.p.), at an interval of 48 ± 2 h for 43 days (21 injections). Nerolidol was administered daily in three doses (12.5, 25 and 50 mg/kg) along with alternate day PTZ injection. To access behavioral comorbidities, animals were subjected to tail suspension test (TST) and passive shock avoidance (PSA) test to evaluate the associated depression and memory impairment respectively on the last day of PTZ administration. Following behavioral assessment, neurotransmitter level and oxidative stress markers were evaluated in brain. The results showed that nerolidol significantly suppressed the progression of kindling. Also, nerolidol ameliorates the kindling associated depression and memory impairment as indicated by decreased immobility time and increased step down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complimented with corresponding neurochemical and oxidative stress markers changes. In conclusion, the results of present study showed that nerolidol treatment has protective effect against PTZ-induced kindling and associated oxidative stress and behavioral comorbidities.

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References

  1. WHO (2015) Epilepsy. Fact sheet no. 999. World Health Organization

  2. Sehar N, Agarwal NB, Vohora D, Raisuddin S (2015) Atorvastatin prevents development of kindling by modulating hippocampal levels of dopamine, glutamate, and GABA in mice. Epilepsy Behav 42:48–53

    Article  PubMed  Google Scholar 

  3. Coelho VR, Vieira CG, de Souza LP, Moyses F, Basso C, Papke DK, Pires TR, Pereira P, Siqueira IR, Picada JN (2015) Antiepileptogenic, antioxidant and genotoxic evaluation of rosmarinic acid and its metabolite caffeic acid in mice. Life Sci 122:65–71

    Article  CAS  PubMed  Google Scholar 

  4. Singh P, Singh D, Goel RK (2014) Ficus religiosa L. figs—a potential herbal adjuvant to phenytoin for improved management of epilepsy and associated behavioral comorbidities. Epilepsy Behav 41:171–178

    Article  PubMed  Google Scholar 

  5. Glauser TA (2004) Effects of antiepileptic medications on psychiatric and behavioral comorbidities in children and adolescents with epilepsy. Epilepsy Behav 5:S25–S32

    Article  PubMed  Google Scholar 

  6. Thome-Souza S, Kuczynski E, Assumpcao F Jr, Rzezak P, Fuentes D, Fiore L, Valente KD (2004) Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy? Epilepsy Behav 5:988–994

    Article  PubMed  Google Scholar 

  7. Gupta YK, Veerendra Kumar MH, Srivastava AK (2003) Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol Biochem Behav 74:579–585

    Article  CAS  PubMed  Google Scholar 

  8. Taiwe GS, Moto FCO, Ayissi ERM, Ngoupaye GT, Njapdounke JSK, Nkantchoua GCN, Kouemou N, Oman JPO, Kandeda AK, Pale S, Pahaye D, Ngo Bum E (2015) Effects of a lyophilized aqueous extract of Feretia apodanthera Del. (Rubiaceae) on pentylenetetrazole-induced kindling, oxidative stress, and cognitive impairment in mice. Epilepsy Behav 43:100–108

    Article  CAS  PubMed  Google Scholar 

  9. Shin EJ, Jeong JH, Chung YH, KimWK, Ko KH, Bach JH, Hong JS, Yoneda Y, Kim HC (2011) Role of oxidative stress in epileptic seizures. Neurochem Int 59:122–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tawfik MK (2011) Coenzyme Q10 enhances the anticonvulsant effect of phenytoin in pilocarpine-induced seizures in rats and ameliorates phenytoin-induced cognitive impairment and oxidative stress. Epilepsy Behav 22:671–677

    Article  PubMed  Google Scholar 

  11. Menut C, Lamaty G, Zollo PA, Abondo R, Bessiére JM (1994) Aromatic plants of tropical central Africa. XII. Fruit essential oil of Aframomum pruinosum gagnepain. A potential source of (E)®Nerolidol. J Essent Oil Res 6(1):19–24

    Article  Google Scholar 

  12. Marques AM, Barreto AS, Curvelo JA, Romanos MT, Soares RM, Kaplan MA (2011) Antileishmanial activity of nerolidol-rich essential oil from Piper claussenianum. Rev Bras Farmacogn 21:23–48

    Article  Google Scholar 

  13. Renata P, Limberger, Sobral M, Henriques AT (2005) Intraspecific volatile oil variation in Myrceugenia cucullata (Myrtaceae). Biochem Systemat Ecol 33(3): 287–293

    Article  Google Scholar 

  14. Nogueira Neto JD, de Almeida AA, da Silva Oliveira J, dos Santos PS, de Sousa DP, de Freitas RM (2013) Antioxidant effects of nerolidol in mice hippocampus after open field test. Neurochem Res 38:1861–1870

    Article  CAS  PubMed  Google Scholar 

  15. Klopella FC, Lemos M, Sousa JP, Comunello E, Maistro EL, Bastos JK, de Andradea SF (2007) Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae). Z Naturforsch C 62:537–542

    Google Scholar 

  16. Ferreira FM, Palmeira CM, Oliveira MM, Santos D, Simões AM, Rocha SM, Coimbra MA, Peixoto F (2012) Nerolidol effects on mitochondrial and cellular energetic. Toxicol In Vitro 26(2):189–196

    Article  CAS  PubMed  Google Scholar 

  17. Tung YT, Chua MT, Wang SY, Chang ST (2008) Anti-inflammation activities of essential oil and its constituents from indigenous cinnamon (Cinnamomum osmophloeum) twigs. Bioresour Technol 99:3908–3913

    Article  CAS  PubMed  Google Scholar 

  18. Baxendale S, Holdsworth CJ, Meza Santoscoy PL, Harrison MR, Fox J, Parkin CA, Ingham PW, Cunliffe VT (2012) Identification of compounds with anticonvulsant properties in a zebrafish model of epileptic seizures. Dis Model Mech 5:773–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Goel RK, Kaur D, Pahwa P (2016) Assessment of anxiolytic effect of nerolidol in mice. Indian J Pharmacol (Ahead of Print)

  20. Pahwa P, Goel RK (2016) Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit. Epilepsy Behav 57:196–201

    Article  PubMed  Google Scholar 

  21. Mishra A, Goel RK (2015) Comparative behavioral and neurochemical analysis of phenytoin and valproate treatment on epilepsy induced learning and memory deficit: search for add on therapy. Metab Brain Dis 30(4):951–958

    Article  CAS  PubMed  Google Scholar 

  22. Erakavoic C, Zupan G, Varljen J, Simonic A (2003) Pentylenetetrazol-induced seizures and kindling: changes in free fatty acids, superoxide dismutase, and glutathione peroxidase activity. Neurochem Int 42(2):435–451

    Google Scholar 

  23. Mishra A, Goel RK (2012) Age dependent learning and memory deficit in pentylenetetrazol kindled mice. Eur J Pharmacol 674:315–320

    Article  CAS  PubMed  Google Scholar 

  24. Li J, Geng D, Xu J, Yi LT, Liu Q, Weng LJ (2013) Antidepressant-like effect of macranthol isolated from Illicium dunnianum tutch in mice. Eur J Pharmacol 707(1–3):112–119

    Article  CAS  PubMed  Google Scholar 

  25. Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) 85(3):367–370

    Article  CAS  Google Scholar 

  26. Goel RK, Gawande D, Langunin A, Randhawa P, Mishra A, Poroikov V (2027) 15) Revealing medicinal plants that are useful for the comprehensive management of epilepsy and associated comorbidities through in silico mining of their phytochemical diversity. Planta Med 81(6):495–506

    Google Scholar 

  27. Zapata A, Chefer VI, Shippenberg TS, Denoroy L (2009) Detection and quantification of neurotransmitters in dialysates. Curr Protoc Neurosci 7:1–30

    PubMed  Google Scholar 

  28. Oakes KD, Van der Kraak GJ (2003) Utility of TBARS assay in detecting oxidative stress in white sucker (Catostomus commersoni) populations exposed to pulp mill effluent. Aquat Toxicol 63:447–463

    Article  CAS  PubMed  Google Scholar 

  29. Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J lab Clin Med 61:882–888

    CAS  PubMed  Google Scholar 

  30. Chance B, Maehly AC (1955) Assay of catalase and peroxidases. Met Enzymol 11:764–775

    Article  Google Scholar 

  31. Choudhary KM, Mishra A, Goel RK, Poroikov VV (2013) Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post pentylenetetrazole-kindled mice. Eur J Pharmacol 704:33–40

    Article  CAS  PubMed  Google Scholar 

  32. Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  33. Devi PU, Manocha A, Vohora D (2008) Seizures, antiepileptics, antioxidants and oxidative stress: an insight for researchers. Expert Opin Pharmacother 9(18):3169–3177

    Article  CAS  PubMed  Google Scholar 

  34. Godlevskii LS, Stepanenko KI, Lobasyuk BA, Sarakhan EV, Bobkova LM (2004) The effects of electrical stimulation of the paleocerebellar cortex on penicillin-induced convulsive activity in rats. Neurosci Behav Physiol 34:797–802

    Article  CAS  PubMed  Google Scholar 

  35. Sudha K, Ashalatha VR, Rao A (2001) Oxidative stress and antioxidants in epilepsy. Clin Chimica Acta 303:19–24

    Article  CAS  Google Scholar 

  36. Zhao RR, Xu XC, Xu F, Zhang WL, Zhang WL, Liu LM (2014) Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice. Biochem Biophys Res Commun 448:414–417

    Article  CAS  PubMed  Google Scholar 

  37. Agarwal NB, Jain S, Agarwal NK, Mediratta PK, Sharma KK (2011) Modulation of pentylenetetrazol-induced kindling and oxidative stress by curcumin in mice. Phytomedicine 18:756–759

    Article  CAS  PubMed  Google Scholar 

  38. Mishra A, Goel RK (2014) Adjuvant anticholinesterase therapy for the management of epilepsy-induced memory deficit: a critical pre-clinical study. Basic Clin Pharmacol Toxicol 115(6):512–517

    Article  CAS  PubMed  Google Scholar 

  39. Takechi K, Suemaru K, Kawasaki H, Araki H (2012) Impaired memory following repeated pentylenetetrazol treatments in kindled mice. Yakugaku Zasshi 132(2):179–182

    Article  CAS  PubMed  Google Scholar 

  40. Epps SA, Weinshenker D (2013) Rhythm and blues: animal models of epilepsy and depression comorbidity. Biochem Pharmacol 85(2):135–146

    Article  CAS  PubMed  Google Scholar 

  41. McIntyre DC, Edson N (1982) Effect of norepinephrine depletion on dorsal hippocampus kindling in rats. Exp Neurol 77:700–704

    Article  CAS  PubMed  Google Scholar 

  42. Szyndler J, Rok P, Maciejak P (2002) Effects of pentylenetetrazol induced kindling of seizures on rat emotional behavior and brain monoaminergic systems. Pharmacol Biochem Behav 73:851–861

    Article  CAS  PubMed  Google Scholar 

  43. Singh D, Mishra A, Goel RK (2013) Effect of saponin fraction from Ficus religiosa on memory deficit, behavioral and biochemical impairments in pentylenetetrazol kindled mice. Epilepsy Behav 27(1):206–211

    Article  PubMed  Google Scholar 

  44. Sudha K, Rao AV, Rao A (2002) Oxidative stress and antioxidants in epilepsy. Clin Chim Acta 303:19–24

    Article  Google Scholar 

  45. Waldbaum S, Patel M (2010) Mitochondrial dysfunction and oxidative stress: a contributing link to acquired epilepsy? J Bioenerg Biomembr 42:449–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Becker A, Grecksch G, Ruthrich HL, Pohle W, Marx B, Matthies H (1992) Kindling and its consequences on learning in rats. Behav Neural Biol 57:37–43

    Article  CAS  PubMed  Google Scholar 

  47. Ahmad S, Fowler LJ, Whitton PS (2005) Effects of combined lamotrigine and valproate on basal and stimulated extracellular amino acids and monoamines in the hippocampus of freely moving rats. Naunyn Schmiedebergs Arch Pharmacol 371:1–8

    Article  CAS  PubMed  Google Scholar 

  48. Trivedi MH, Kurian BT (2007) Managing depressive disorders in patients with epilepsy. Psychiatry 4(1):26–34

    PubMed  PubMed Central  Google Scholar 

  49. Kanner AM (2003) Depression in epilepsy is much more than a reactive process. Epilepsy Curr 3(6):202–203

    Article  PubMed  PubMed Central  Google Scholar 

  50. Elhwuegi AS (2004) Central monoamines and their role in major depression. Prog Neuropsychopharmacol Biol Psychiatry 28:435–451

    Article  CAS  PubMed  Google Scholar 

  51. Ng F, Berk M, Dean O, Bush AI (2008) Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 11(6):851–876

    Article  CAS  PubMed  Google Scholar 

  52. Nazıroğlu M, Yürekli VA (2013) Effects of antiepileptic drugs on antioxidant and oxidant molecular pathways: focus on trace elements. Cell Mol Neurobiol 33(5):589–599

    Article  PubMed  Google Scholar 

  53. El Zahaf NA, Salem Elhwuegi A (2014) The effect of GABAmimetics on the duration of immobility in the forced swim test in albino mice. Libyan J Med 9:234–280

    Google Scholar 

  54. Delva NJ, Brooks DL, Franklin M, al-Said K, Hawken ER, Merali Z, Lawson JS, Ravindran AV (2002) Effects of short term administration of valproate on serotonin-1 A and dopamine receptor function in healthy subjects. J Psychiatry Neurosci 27(6):429–437

    PubMed  PubMed Central  Google Scholar 

  55. Kaur H, Singh D, Singh B, Goel RK (2010) Anti-amnesic effect of Ficus religiosa in scopolamine-induced anterograde and retrograde amnesia. Pharm Biol 48:234–240

    Article  CAS  PubMed  Google Scholar 

  56. Khurana N, Ishar MPS, Gajbiya A, Goel RK (2011) PASS assisted prediction and pharmacological evaluation of novel nicotinic analogues for nootropic activity in mice. Eur J Pharmacol 662:22–30

    Article  CAS  PubMed  Google Scholar 

  57. Blokland A (1995) Acetylcholine: a neurotransmitter for learning and memory? Brain Res Rev 21:285–300

    Article  CAS  PubMed  Google Scholar 

  58. Arnsten AF (1998) Catecholamine modulation of prefrontal cortical cognitive function. Trends Cogn Sci 2(11):436–447

    Article  CAS  PubMed  Google Scholar 

  59. Dröge W, Schipper HM (2007) Oxidative stress and aberrant signaling in aging and cognitive decline. Aging Cell 6(3):361–370

    Article  PubMed  PubMed Central  Google Scholar 

  60. Ahmad A, Rasheed N, Banu N, Palit G (2010) Alterations in monoamine levels and oxidative systems in frontal cortex, striatum, and hippocampus of the rat brain during chronic unpredictable stress. Stress 13(4):355–364

    Article  PubMed  Google Scholar 

  61. Maher P, Davis JB (1996) The role of monoamine metabolism in oxidative glutamate toxicity. J Neurosci 16(20):6394–6401

    CAS  PubMed  Google Scholar 

  62. Sultana R, Butterfield DA (2010) Role of oxidative stress in the progression of Alzheimer’s disease. J Alzheimers Dis 19(1):341–353

    PubMed  Google Scholar 

  63. Gupta YK, Veerendra Kumar MH, Srivastava AK (2003) Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol Biochem Behav 74(3):579–585

    Article  CAS  PubMed  Google Scholar 

  64. Eddy CM, Rickards HE, Cavanna AE (2011) The cognitive impact of antiepileptic drugs. Ther Adv Neurol Disord 4(6):385–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Garcia CS (2012) Depression in temporal lobe epilepsy: a review of prevalence, clinical features, and management considerations. Epilepsy Res Treat 1–13

  66. Verrotti A, Scardapane A, Franzoni E, Manco R, Chiarelli F (2008) Increased oxidative stress in epileptic children treated with valproic acid. Epilepsy Res 78(2–3):171–177

    Article  CAS  PubMed  Google Scholar 

  67. Martinc B, Grabnar I, Vovk T (2012) The role of reactive species in epileptogenesis and influence of antiepileptic drug therapy on oxidative stress. Curr Neuropharmacol 10(4):328–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to acknowledge the Council of Scientific and Industrial Research (CSIR) for the waters-HPLC system for neurochemical estimations vide No: 38 (1339/12/EMR-II) and Department of Pharmaceutical Science and Drug Research, Punjabi University, Patiala to provide infrastructures and other facilities to carry out research work.

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Correspondence to Rajesh Kumar Goel.

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Kaur, D., Pahwa, P. & Goel, R.K. Protective Effect of Nerolidol Against Pentylenetetrazol-Induced Kindling, Oxidative Stress and Associated Behavioral Comorbidities in Mice. Neurochem Res 41, 2859–2867 (2016). https://doi.org/10.1007/s11064-016-2001-2

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  • DOI: https://doi.org/10.1007/s11064-016-2001-2

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