##submission.viewingPreview##

اثر نانوکورکومین خوراکی بر تشنج ناشی از پنتیلن تترازول داخل صفاقی و الگوی فسفوریلاسیون CaMKII در هیپوکامپ موش سوری نر

نویسندگان

  • لیلا معزی گروه فارماکولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران. orcid https://orcid.org/0000-0002-6990-9138
  • فاطمه پیرسلامی گروه فارماکولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران. orcid https://orcid.org/0000-0002-0100-0809
  • زهرا اسماعیلی مرکز تحقیقات علوم اعصاب شیراز، دانشگاه علوم پزشکی شیراز، شیراز، ایران. - مرکز تحقیقات علوم اعصاب، انستیتو نوروفارماکولوژی، دانشگاه علوم پزشکی کرمان، کرمان، ایران. orcid https://orcid.org/0000-0003-3776-236X
  • مریم موسوی مرکز تحقیقات نانوفناوری در علوم زیستی و پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران. orcid https://orcid.org/0000-0001-6943-477X

DOI::

https://doi.org/10.22100/jkh.v18i3.3061

چکیده

مقدمه: مطالعات قبلی حاکی از آن است که تبدیل کورکومین به فرم نانو ذره می تواند موجب افزایش اثر درمانی آن در مدل های تشنج شود. نشان داده شده است که تغییرات پروتئین کیناز II وابسته به کلسیم/کالمودولین (CaMKII) با بعضی از مدل های تجربی صرع مرتبط است.  مطالعه حاضر با هدف بررسی الگوی CaMKII هیپوکامپ متعاقب اثر درمانی نانوکورکومین در مدل تشنج ناشی از پنتیلن تترازول (PTZ) انجام گردید. مواد و روش ها: نانوکورکومین بر مبنای آلبومین سرم گاوی تولید شد و  در دوزهای 50 و 100 میلی گرم/ کیلوگرم به صورت خوراکی(گاواژ) به موش های سوری نر نژاد NMRI  با وزن 30-25 گرم تجویز گردید. یک ساعت بعد PTZ با دوز 85 میلی­گرم/کیلوگرم به صورت داخل صفاقی به حیوان تجویز شد. متعاقب تزریق PTZ داخل صفاقی مدت زمان وقوع میوکلونوس، کلونوس، وقوع تشنج تونیک عمومی و میزان مرگ و میر در موشهای سوری نر ثبت گردید. پس از بررسی الگوی رفتاری  تشنج ، حیوانات بیهوش شده کشته شدند و میزان فرمهای فسفریله و کامل CaMKII هیپوکامپ آنان از طریق روش وسترن بلات تعیین گردید. نتایج: نتایج نشان داد که تجویز خوراکی نانوکورکومین تولیدشده با BSA در دوزهای 50 و 100 میلی گرم بر کیلوگرم، در مقایسه با کورکومین طبیعی به طور قابل توجهی تشنج متعاقب PTZ را بهبود داد. در همه گروه ها تشنج موجب افزایش فسفوریلاسیون CaMKII هیپوکامپ شد و نانوکورکومین آن را تعدیل نکرد. نتیجه گیری:  یافته های این مطالعه نشان داد که اثر درمانی نانوکورکومین در مدل تشنج ناشی از پنتیلن تترازول ارتباطی با تغییر الگوی فعالیت  CaMKII هیپوکامپ ندارد.

مراجع

Györffy B, Kovács Z, Gulyássy P, Simor A, Völgyi K, Orbán G, et al. Brain protein expression changes in WAG/Rij rats, a genetic rat model of absence epilepsy after peripheral lipopolysaccharide treatment. Brain, behavior, and immunity 2014;35:86-95. doi: 10.1016/j.bbi.2013.09.001

Tang F, Hartz AMS, Bauer B. Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers. Front Neurol 2017;8:301. doi: 10.3389/fneur.2017.00301

Vidaurre J, Gedela S, Yarosz S. Antiepileptic Drugs and Liver Disease. Pediatric Neurology 2017;77:23-36. doi: https://doi.org/10.1016/j.pediatrneurol.2017.09.013

Buckmaster PS, Wen X, Toyoda I, Gulland FM, Van Bonn W. Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus). The Journal of comparative neurology 2014;522:1691-706. doi: 10.1002/cne.23509

Blair RE, Churn SB, Sombati S, Lou JK, DeLorenzo RJ. Long-lasting decrease in neuronal Ca2+/calmodulin-dependent protein kinase II activity in a hippocampal neuronal culture model of spontaneous recurrent seizures. Brain research 1999;851:54-65. doi:

Bronstein J, Farber D, Wasterlain C. Decreased calmodulin kinase activity after status epilepticus. Neurochemical research 1988;13:83-6. doi:

Dong Y, Rosenberg HC. Brief seizure activity alters Ca2+/calmodulin dependent protein kinase II dephosphorylation and subcellular distribution in rat brain for several hours. Neurosci Lett 2004;357:95-8. doi: 10.1016/j.neulet.2003.11.069

Yamagata Y, Imoto K, Obata K. A mechanism for the inactivation of Ca2+/calmodulin-dependent protein kinase II during prolonged seizure activity and its consequence after the recovery from seizure activity in rats in vivo. Neuroscience 2006;140:981-92. doi: 10.1016/j.neuroscience.2006.02.054

Lee MC, Ban SS, Woo YJ, Kim SU. Calcium/calmodulin kinase II activity of hippocampus in kainate-induced epilepsy. Journal of Korean medical science 2001;16:643-8. doi: 10.3346/jkms.2001.16.5.643

Weeber EJ, Jiang YH, Elgersma Y, Varga AW, Carrasquillo Y, Brown SE, et al. Derangements of hippocampal calcium/calmodulin-dependent protein kinase II in a mouse model for Angelman mental retardation syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience 2003;23:2634-44. doi: 10.1523/jneurosci.23-07-02634.2003

Zha X-m, Dailey ME, Green SH. Role of Ca2+/calmodulin-dependent protein kinase II in dendritic spine remodeling during epileptiform activity in vitro. J Neurosci Res 2009;87:1969-79. doi: 10.1002/jnr.22033

Ebrahimi F, Sadr SS. Assessment of the protective effect of KN-93 drug in systemic epilepsy disorders induced by pilocarpine in male rat. 2019;120:15906-14. doi: 10.1002/jcb.28864

Liu X-B, Murray KD. Neuronal excitability and calcium/calmodulin-dependent protein kinase type II: Location, location, location. Epilepsia 2012;53:45-52. doi: https://doi.org/10.1111/j.1528-1167.2012.03474.x

Lie AA, Blümcke I, Beck H, Schramm J, Wiestler OD, Elger CE. Altered patterns of Ca2+/calmodulin-dependent protein kinase II and calcineurin immunoreactivity in the hippocampus of patients with temporal lobe epilepsy. Journal of neuropathology and experimental neurology 1998;57:1078-88. doi: 10.1097/00005072-199811000-00011

Kocaadam B, Sanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Critical reviews in food science and nutrition 2017;57:2889-95. doi: 10.1080/10408398.2015.1077195

Kumar V, Prakash C, Singh R, Sharma D. Curcumin's antiepileptic effect, and alterations in Na(v)1.1 and Na(v)1.6 expression in iron-induced epilepsy. Epilepsy research 2019;150:7-16. doi: 10.1016/j.eplepsyres.2018.12.007

Akula KK, Kulkarni SK. Effect of curcumin against pentylenetetrazol-induced seizure threshold in mice: possible involvement of adenosine A1 receptors. Phytotherapy research : PTR 2014;28:714-21. doi: 10.1002/ptr.5048

Arbabi Jahan A, Rad A, Ghanbarabadi M, Amin B, Mohammad-Zadeh M. The role of serotonin and its receptors on the anticonvulsant effect of curcumin in pentylenetetrazol-induced seizures. Life sciences 2018;211:252-60. doi: 10.1016/j.lfs.2018.09.007

Choudhary KM, Mishra A, Poroikov VV, Goel RK. Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post-pentylenetetrazole-kindled mice. European journal of pharmacology 2013;704:33-40. doi: 10.1016/j.ejphar.2013.02.012

Kiasalari Z, Roghani M, Khalili M, Rahmati B, Baluchnejadmojarad T. Antiepileptogenic effect of curcumin on kainate-induced model of temporal lobe epilepsy. Pharmaceutical biology 2013;51:1572-8. doi: 10.3109/13880209.2013.803128

Du P, Tang HY, Li X, Lin HJ, Peng WF, Ma Y, et al. Anticonvulsive and antioxidant effects of curcumin on pilocarpine-induced seizures in rats. Chinese medical journal 2012;125:1975-9. doi:

Kaur H, Bal A, Sandhir R. Curcumin supplementation improves mitochondrial and behavioral deficits in experimental model of chronic epilepsy. Pharmacology, biochemistry, and behavior 2014;125:55-64. doi: 10.1016/j.pbb.2014.08.001

Sumanont Y, Murakami Y, Tohda M, Vajragupta O, Watanabe H, Matsumoto K. Effects of manganese complexes of curcumin and diacetylcurcumin on kainic acid-induced neurotoxic responses in the rat hippocampus. Biological & pharmaceutical bulletin 2007;30:1732-9. doi: 10.1248/bpb.30.1732

Drion CM, Borm LE, Kooijman L, Aronica E, Wadman WJ, Hartog AF, et al. Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats. Epilepsia 2016;57:688-97. doi: 10.1111/epi.13345

Tønnesen HH. Solubility, chemical and photochemical stability of curcumin in surfactant solutions. Studies of curcumin and curcuminoids, XXVIII. Die Pharmazie 2002;57:820-4. doi:

Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Advances in experimental medicine and biology 2007;595:1-75. doi: 10.1007/978-0-387-46401-5_1

Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochemical pharmacology 2008;75:787-809. doi: 10.1016/j.bcp.2007.08.016

Flora G, Gupta D, Tiwari A. Nanocurcumin: a promising therapeutic advancement over native curcumin. Critical reviews in therapeutic drug carrier systems 2013;30:331-68. doi: 10.1615/critrevtherdrugcarriersyst.2013007236

Hashemian M, Anissian D, Ghasemi-Kasman M, Akbari A, Khalili-Fomeshi M, Ghasemi S, et al. Curcumin-loaded chitosan-alginate-STPP nanoparticles ameliorate memory deficits and reduce glial activation in pentylenetetrazol-induced kindling model of epilepsy. Progress in neuro-psychopharmacology & biological psychiatry 2017;79:462-71. doi: 10.1016/j.pnpbp.2017.07.025

Agarwal NB, Jain S, Nagpal D, Agarwal NK, Mediratta PK, Sharma KK. Liposomal formulation of curcumin attenuates seizures in different experimental models of epilepsy in mice. Fundamental & clinical pharmacology 2013;27:169-72. doi: 10.1111/j.1472-8206.2011.01002.x

Moezi L, Ashjazadeh N, Rezapanah S, Pirsalami F, Esmaeili Z, Soukhaklari R, et al. Anticonvulsant effect of acute curcumin nanoparticle on pentylenetetrazole-induced seizures in mice: non-involvement of jnk restoration. Physiology and Pharmacology (Iran) 2021;25:36-46. doi: 10.32598/ppj.25.1.80

Aniesrani Delfiya DS, Thangavel K, Amirtham D. Preparation of Curcumin Loaded Egg Albumin Nanoparticles Using Acetone and Optimization of Desolvation Process. The protein journal 2016;35:124-35. doi: 10.1007/s10930-016-9652-3

Jithan A, Madhavi K, Madhavi M, Prabhakar K. Preparation and characterization of albumin nanoparticles encapsulating curcumin intended for the treatment of breast cancer. International journal of pharmaceutical investigation 2011;1:119-25. doi: 10.4103/2230-973x.82432

Kim TH, Jiang HH, Youn YS, Park CW, Tak KK, Lee S, et al. Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity. International journal of pharmaceutics 2011;403:285-91. doi: 10.1016/j.ijpharm.2010.10.041

SoukhakLari R, Moezi L, Pirsalami F, Moosavi M. The Effect of BSA-Based Curcumin Nanoparticles on Memory and Hippocampal MMP-2, MMP-9, and MAPKs in Adult Mice. Journal of molecular neuroscience : MN 2018;65:319-26. doi: 10.1007/s12031-018-1104-4

Kupferberg H. Animal models used in the screening of antiepileptic drugs. Epilepsia 2001;42 Suppl 4:7-12. doi:

Löscher W, Fiedler M. The role of technical, biological, and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. VII. Seasonal influences on anticonvulsant drug actions in mouse models of generalized seizures. Epilepsy research 2000;38:231-48. doi: 10.1016/s0920-1211(99)00095-9

Löscher W, Lehmann H. L-deprenyl (selegiline) exerts anticonvulsant effects against different seizure types in mice. The Journal of pharmacology and experimental therapeutics 1996;277:1410-7. doi:

Shafaroodi H, Moezi L, Ghorbani H, Zaeri M, Hassanpour S, Hassanipour M, et al. Sub-chronic treatment with pioglitazone exerts anti-convulsant effects in pentylenetetrazole-induced seizures of mice: The role of nitric oxide. Brain research bulletin 2012;87:544-50. doi: 10.1016/j.brainresbull.2012.02.001

Nam SM, Kwon HJ, Kim W, Kim JW, Hahn KR, Jung HY, et al. Changes of myelin basic protein in the hippocampus of an animal model of type 2 diabetes. Lab Anim Res 2018;34:176-84. doi: 10.5625/lar.2018.34.4.176

Xu B, Lang L-M, Li S-Z, Guo J-R, Wang J-F, Wang D, et al. Cortisol Excess-Mediated Mitochondrial Damage Induced Hippocampal Neuronal Apoptosis in Mice Following Cold Exposure. Cells 2019;8:612. doi: 10.3390/cells8060612

Yun D, Jeon M-T, Kim H-J, Moon GJ, Lee S, Ha CM, et al. Induction of GDNF and GFRα-1 Following AAV1-Rheb(S16H) Administration in the Hippocampus in vivo. Exp Neurobiol 2020;29:164-75. doi: 10.5607/en19075

Zhu Y, Zhang Q, Zhang W, Li N, Dai Y, Tu J, et al. Protective Effect of 17β-Estradiol Upon Hippocampal Spine Density and Cognitive Function in an Animal Model of Vascular Dementia. Scientific reports 2017;7:42660-. doi: 10.1038/srep42660

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. The Journal of biological chemistry 1951;193:265-75. doi:

Amiri E, Ghasemi R, Moosavi M. Agmatine Protects Against 6-OHDA-Induced Apoptosis, and ERK and Akt/GSK Disruption in SH-SY5Y Cells. Cellular and molecular neurobiology 2016;36:829-38. doi: 10.1007/s10571-015-0266-7

Moosavi M, Abbasi L, Zarifkar A, Rastegar K. The role of nitric oxide in spatial memory stages, hippocampal ERK and CaMKII phosphorylation. Pharmacology, biochemistry, and behavior 2014;122:164-72. doi: 10.1016/j.pbb.2014.03.021

Rein MJ, Renouf M, Cruz-Hernandez C, Actis-Goretta L, Thakkar SK, da Silva Pinto M. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy. British journal of clinical pharmacology 2013;75:588-602. doi: 10.1111/j.1365-2125.2012.04425.x

Scheepens A, Tan K, Paxton JW. Improving the oral bioavailability of beneficial polyphenols through designed synergies. Genes & nutrition 2010;5:75-87. doi: 10.1007/s12263-009-0148-z

Wahlstrom B, Blennow G. A study on the fate of curcumin in the rat. Acta pharmacologica et toxicologica 1978;43:86-92. doi: 10.1111/j.1600-0773.1978.tb02240.x

Rogawski MA. Molecular targets versus models for new antiepileptic drug discovery. Epilepsy research 2006;68:22-8. doi: 10.1016/j.eplepsyres.2005.09.012

Huang RQ, Bell-Horner CL, Dibas MI, Covey DF, Drewe JA, Dillon GH. Pentylenetetrazole-induced inhibition of recombinant gamma-aminobutyric acid type A (GABA(A)) receptors: mechanism and site of action. The Journal of pharmacology and experimental therapeutics 2001;298:986-95. doi:

Löscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure 2011;20:359-68. doi: 10.1016/j.seizure.2011.01.003

Mandhane SN, Aavula K, Rajamannar T. Timed pentylenetetrazol infusion test: a comparative analysis with s.c.PTZ and MES models of anticonvulsant screening in mice. Seizure 2007;16:636-44. doi: 10.1016/j.seizure.2007.05.005

Sookhaklari R, Geramizadeh B, Abkar M, Moosavi M. The neuroprotective effect of BSA-based nanocurcumin against 6-OHDA-induced cell death in SH-SY5Y cells. Basic and clinical neuroscience 2019;9:92-100. doi: 10.32598/bcn.9.10.255

SoukhakLari R, Moezi L. Curcumin-Loaded BSA Nanoparticles Protect More Efficiently Than Natural Curcumin Against Scopolamine-Induced Memory Retrieval Deficit. 2019;10:157-64. doi: 10.32598/bcn.9.10.255

SoukhakLari R, Moezi L, Pirsalami F, Moosavi M. The Effect of BSA-Based Curcumin Nanoparticles on Memory and Hippocampal MMP-2, MMP-9, and MAPKs in Adult Mice. 2018;65:319-26. doi: 10.1007/s12031-018-1104-4

Khadrawy YA, Sawie HG, Hosny EN. Neuroprotective effect of curcumin nanoparticles against rat model of status epilepticus induced by pilocarpine. Journal of complementary & integrative medicine 2018;15. doi: 10.1515/jcim-2017-0117

McNamara JO, Huang YZ, Leonard AS. Molecular signaling mechanisms underlying epileptogenesis. Science's STKE : signal transduction knowledge environment 2006;2006:re12. doi: 10.1126/stke.3562006re12

Lie AA, Sommersberg B, Elger CE. Analysis of pThr286-CaMKII and CaMKII immunohistochemistry in the hippocampus of patients with temporal lobe epilepsy. Epilepsy research 2005;67:13-23. doi: https://doi.org/10.1016/j.eplepsyres.2005.06.009

Ghosh A, Greenberg ME. Calcium signaling in neurons: molecular mechanisms and cellular consequences. Science (New York, NY) 1995;268:239-47. doi: 10.1126/science.7716515

Choi DW. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends in neurosciences 1988;11:465-9. doi: 10.1016/0166-2236(88)90200-7

Delorenzo RJ, Sun DA, Deshpande LS. Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintainance of epilepsy. Pharmacology & therapeutics 2005;105:229-66. doi: 10.1016/j.pharmthera.2004.10.004

Carter DS, Haider SN, Blair RE, Deshpande LS, Sombati S, DeLorenzo RJ. Altered calcium/calmodulin kinase II activity changes calcium homeostasis that underlies epileptiform activity in hippocampal neurons in culture. The Journal of pharmacology and experimental therapeutics 2006;319:1021-31. doi: 10.1124/jpet.106.110403

Lisman J, Yasuda R, Raghavachari S. Mechanisms of CaMKII action in long-term potentiation. Nature reviews Neuroscience 2012;13:169-82. doi: 10.1038/nrn3192

Mayadevi M, Sherin DR, Keerthi VS, Rajasekharan KN, Omkumar RV. Curcumin is an inhibitor of calcium/calmodulin dependent protein kinase II. Bioorganic & Medicinal Chemistry 2012;20:6040-7. doi: https://doi.org/10.1016/j.bmc.2012.08.029

شماره

نوع مقاله

مقاله پژوهشي

مقالات بیشتر خوانده شده از همین نویسنده

<< < 6 7 8 9 10 11 12 13 14 15 > >>