nach oben

Metabolic Brain Disease

Erschienen in:

14.11.2019 | Original Article

Nanoformulated ellagic acid ameliorates pentylenetetrazol-induced experimental epileptic seizures by modulating oxidative stress, inflammatory cytokines and apoptosis in the brains of male mice

verfasst von: Mohamed A. El-Missiry, Azza I. Othman, Maher A. Amer, Mohammed Sedki, Sara M. Ali, Ibrahim M. El-Sherbiny

Erschienen in: Metabolic Brain Disease | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

The present study evaluated the neuroprotective and antiepileptic efficacy of ellagic acid (EA) encapsulated in calcium-alginate nanoparticles (Ca²⁺-ALG NPs) in pentylenetetrazol (PTZ)-induced seizures in male mice. EA was encapsulated in ALG NPs using a nanospray drying method followed by ionotropic crosslinking with Ca²⁺. Characterization of the developed Ca²⁺-crosslinked EA-ALG NPs showed spherical, high stability NPs; successful loading of EA within crosslinked ALG NPs; and sustained release of EA. Male Swiss albino mice were divided into ten groups as follows; Group I- (control), Group II (50 mg EA /kg) - (EA), Group III polyethylene glycol (PEG), Group IV EA NPs (50 mg/kg) - (EA NP), Group (50 mg/kg alginate) V void V NPs - (void NPs), Group VI: (37.5 PTZ mg/kg) -(PTZ), Group VII: PTZ and EA – (PTZ-EA). Group VIII: animals received PTZ and PEG concurrently (PTZ-PEG). Group IX; animals received PTZ and void NPs concurrently - (PTZ-void). Group X: animals received PTZ and EA NPs concurrently (PTZ-EA NPs). PTZ was used to induce experimental epilepsy. Ca²⁺-ALG NPs prevented seizures throughout the experimental period and had a more prominent effect than free EA did. Ca²⁺-ALG NPs prevented increased glutamate, decreased GABA concentrations and ameliorated increased amyloid-β and homocysteine levels in the serum and brain. Ca²⁺-EA-ALG NPs were superior to free EA in improving increased IL-6 and TNF-α. Ca²⁺-ALG NPs ameliorated PTZ-induced oxidative stress, as evidenced by decreased 4HNE levels and enhanced GSH, GR and GPx levels in the brain. These changes were accompanied by amelioration of apoptosis and its regulating proteins, including Cytochrome C, P53, Bax, Bcl2 and caspase-3 and caspase-9, and protected against DNA damage. Histological examination of the hippocampus confirmed that the neuroprotective effect of Ca²⁺-EA-ALG NPs was superior and more effective than that of free EA.

Aghaie T, Jazayeri MH, Manian M, Khani L, Erfani M, Rezayi M, Ferns GA, Avan A (2019) Gold nanoparticle and polyethylene glycol in neural regeneration in the treatment of neurodegenerative diseases. J Cell Biochem 120:2749–2755PubMed

Aluani D, Tzankova V, Kondeva-Burdina M, Yordanov Y, Nikolova E, Odzhakov F, Apostolov A, Markova T, Yoncheva K (2017) Capital IE, Cyrillicvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin. Int J Biol Macromol 103:771–782PubMed

Ana R, Mendes M, Sousa J, Pais A, Falcao A, Fortuna A, Vitorino C (2019) Rethinking carbamazepine oral delivery using polymer-lipid hybrid nanoparticles. Int J Pharm 554:352–365PubMed

Arulmozhi V, Pandian K, Mirunalini S (2013) Ellagic acid encapsulated chitosan nanoparticles for drug delivery system in human oral cancer cell line (KB). Colloids Surf B Biointerfaces 110:313–320PubMed

Bala I, Bhardwaj V, Hariharan S, Kharade SV, Roy N, Ravi Kumar MN (2006) Sustained release nanoparticulate formulation containing antioxidant-ellagic acid as potential prophylaxis system for oral administration. J Drug Target 14:27–34PubMed

Baldelli E, Leo G, Andreoli N, Fuxe K, Biagini G, Agnati LF (2010) Homocysteine potentiates seizures and cell loss induced by pilocarpine treatment. NeuroMolecular Med 12:248–259PubMed

Baluchnejadmojarad T, Rabiee N, Zabihnejad S, Roghani M (2017) Ellagic acid exerts protective effect in intrastriatal 6-hydroxydopamine rat model of Parkinson's disease: possible involvement of ERbeta/Nrf2/HO-1 signaling. Brain Res 1662:23–30PubMed

Bett GC, Lis A, Wersinger SR, Baizer JS, Duffey ME, Rasmusson RL (2012) A mouse model of Timothy syndrome: a complex autistic disorder resulting from a point mutation in Cav1. 2. N Am J Med Sci 5:–135

Campanella M, Sciorati C, Tarozzo G, Beltramo M (2002) Flow cytometric analysis of inflammatory cells in ischemic rat brain. Stroke 33:586–592PubMed

Cavalcante TMB, De Melo JMAJ, Lopes LB, Bessa MC, Santos JG, Vasconcelos LC, Vieira Neto AE, Borges LTN, Fonteles MMF, Chaves Filho AJM, Macedo D, Campos AR, Aguiar CCT, Vasconcelos SMM (2019) Ivabradine possesses anticonvulsant and neuroprotective action in mice. Biomedicine & pharmacotherapy 109:2499–2512

Chen L, Shen R, Komasa S, Xue Y, Jin B, Hou Y, Okazaki J, Gao J (2017) Drug-loadable calcium alginate hydrogel system for use in oral bone tissue repair. Int J Mol Sci 18:989PubMedCentral

Chong ZZ, Kang JQ, Maiese K (2004) Essential cellular regulatory elements of oxidative stress in early and late phases of apoptosis in the central nervous system. Antioxid Redox Signal 6:277–287PubMed

Corda MG, Giorgi O, Longoni B, Orlandi M, Biggio G (1990) Decrease in the function of the gamma-aminobutyric acid-coupled chloride channel produced by the repeated administration of pentylenetetrazol to rats. J Neurochem 55:1216–1221PubMed

Davoudi M, Shojaei A, Palizvan MR, Javan M, Mirnajafi-Zadeh J (2013) Comparison between standard protocol and a novel window protocol for induction of pentylenetetrazol kindled seizures in the rat. Epilepsy Res 106:54–63PubMed

Dhingra D, Jangra A (2014) Antiepileptic activity of ellagic acid, a naturally occurring polyphenolic compound, in mice. J Funct Foods 10:364–369

Erta M, Quintana A, Hidalgo J (2012) Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 8:1254–1266PubMedPubMedCentral

Farbood Y, Sarkaki A, Dianat M, Khodadadi A, Haddad MK, Mashhadizadeh S (2015) Ellagic acid prevents cognitive and hippocampal long-term potentiation deficits and brain inflammation in rat with traumatic brain injury. Life Sci 124:120–127PubMed

Fu Y, Tang M, Bai L, Fan Y (2016) The role of apoptosis inducing factor in the apoptosis of retinal pigment epithelium cells induced by oxidative stress. Cell Mol Biol (Noisy-le-grand) 62:36–41

Garcia-Nino WR, Zazueta C (2015) Ellagic acid: pharmacological activities and molecular mechanisms involved in liver protection. Pharmacol Res 97:84–103PubMed

George M, Abraham TE (2006) Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan-a review. J Control Release 114:1–14PubMed

Goh CH, Heng PWS, Chan LW (2012) Alginates as a useful natural polymer for microencapsulation and therapeutic applications. Carbohydr Polym 88:1–12

Golechha M, Sarangal V, Bhatia J, Chaudhry U, Saluja D, Arya DS (2014) Naringin ameliorates pentylenetetrazol-induced seizures and associated oxidative stress, inflammation, and cognitive impairment in rats: possible mechanisms of neuroprotection. Epilepsy Behav. 41:98–102

Goswami SK, Vishwanath M, Gangadarappa SK, Razdan R, Inamdar MN (2014) Efficacy of ellagic acid and sildenafil in diabetes-induced sexual dysfunction. Pharmacogn Mag 10:S581PubMedPubMedCentral

Grasel Fdos S, Ferrao MF, Wolf CR (2016) Development of methodology for identification the nature of the polyphenolic extracts by FTIR associated with multivariate analysis. Spectrochim Acta A Mol Biomol Spectrosc 153:94–101

Gruol DL (2015) IL-6 regulation of synaptic function in the CNS. Neuropharmacology 96:42–54PubMed

Hoda U, Agarwal NB, Vohora D, Parvez S, Raisuddin S (2017) Resveratrol suppressed seizures by attenuating IL-1β, IL1-Ra, IL-6, and TNF-α in the hippocampus and cortex of kindled mice. Nutr Neurosci 20:497–504PubMed

Iino T, Nakahara K, Miki W, Kiso Y, Ogawa Y, Kato S, Takeuchi K (2001) Less damaging effect of whisky in rat stomachs in comparison with pure ethanol. Role of ellagic acid, the nonalcoholic component. Digestion 64:214–221PubMed

Juan WS, Lin HW, Chen YH, Chen HY, Hung YC, Tai SH, Huang SY, Chen TY, Lee EJ (2012) Optimal Percoll concentration facilitates flow cytometric analysis for annexin V/propidium iodine-stained ischemic brain tissues. Cytometry A, 81:400–408

Khadrawy YA, Sawie HG, Hosny EN (2018) Neuroprotective effect of curcumin nanoparticles against rat model of status epilepticus induced by pilocarpine. J Complement Integr Med 15(3):1–10

Kornev VA, Grebenik EA, Solovieva AB, Dmitriev RI, Timashev PS (2018) Hydrogel-assisted neuroregeneration approaches towards brain injury therapy: A state-of-the-art review. Comput Struct Biotechnol J 16:488–502PubMedPubMedCentral

Kumar R, Arora R, Agarwal A, Gupta YK (2018) Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats. J Ethnopharmacol 215:124–131PubMed

Larsen B, Salem DM, Sallam MA, Mishrikey MM, Beltagy AI (2003) Characterization of the alginates from algae harvested at the Egyptian Red Sea coast. Carbohydr Res 338:2325–2336PubMed

Lei F, Xing DM, Xiang L, Zhao YN, Wang W, Zhang LJ, Du LJ (2003) Pharmacokinetic study of ellagic acid in rat after oral administration of pomegranate leaf extract. J Chromatogr B Analyt Technol Biomed Life Sci 796:189–194

Lin TY, Lu CW, Wang SJ, Huang SK (2015) Protective effect of hispidulin on kainic acid-induced seizures and neurotoxicity in rats. Eur J Pharmacol 755:6–15PubMed

Liu Z, Lindemeyer AK, Liang J, Wallner M, Shao XM, Shao Y, Tao Y, Olsen RW (2018) Flavonoids isolated from Tibetan medicines, binding to GABAA receptor and the anticonvulsant activity. Phytomedicine 50:1–7PubMed

Mady FM, Shaker MA (2017) Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles. Int J Nanomedicine 12:7405–7417PubMedPubMedCentral

Mares J, Stopka P, Nohejlova K, Rokyta R (2013) Oxidative stress induced by epileptic seizure and its attenuation by melatonin. Physiol Res 62(Suppl 1):S67–S74PubMed

Mendez-Armenta M, Nava-Ruiz C, Juarez-Rebollar D, Rodriguez-Martinez E, Gomez PY (2014) Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxidative Med Cell Longev 2014:293689

Moreira AC, Branco AF, Sampaio SF, Cunha-Oliveira T, Martins TR, Holy J, Oliveira PJ, Sardao VA (2014) Mitochondrial apoptosis-inducing factor is involved in doxorubicin-induced toxicity on H9c2 cardiomyoblasts. Biochim Biophys Acta 1842:2468–2478PubMed

Mukhopadhyay B, Gavel R, Gongopadhyay AN, Vashistha P, Rani A, Mishra SP (2016) Correlation of Oxidative Damage with Pro-Inflammatory Markers (IL-6, TNF-alpha) in Meningocele. J Clin Diagn Res 10:BC08–BC10

Musumeci T, Serapide MF, Pellitteri R, Dalpiaz A, Ferraro L, Dal Magro R, Bonaccorso A, Carbone C, Veiga F, Sancini G (2018) Oxcarbazepine free or loaded PLGA nanoparticles as effective intranasal approach to control epileptic seizures in rodents. Eur J Pharm Biopharm 133:309–320PubMed

Obeid R, Herrmann W (2006) Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 580:2994–3005PubMed

Pauletti A, Terrone G, Shekh-Ahmad T, Salamone A, Ravizza T, Rizzi M, Pastore A, Pascente R, Liang LP, Villa BR, Balosso S, Abramov AY, van Vliet EA, Del Giudice E, Aronica E, Antoine DJ, Patel M, Walker MC, Vezzani A (2017) Targeting oxidative stress improves disease outcomes in a rat model of acquired epilepsy. Brain J Neurol 140:1885–1899

Pearson-Smith JN, Patel M (2017) Metabolic dysfunction and oxidative stress in epilepsy. Int J Mol Sci 18PubMedCentral

Pineda E, Shin D, You SJ, Auvin S, Sankar R, Mazarati A (2013) Maternal immune activation promotes hippocampal kindling epileptogenesis in mice. Ann Neurol 74:11–19PubMedPubMedCentral

Prasad DKV, Satyanarayana U, Shaheen U, Prabha TS, Munshi A (2017) Oxidative Stress in the Development of Genetic Generalised Epilepsy: An Observational Study in Southern Indian Population. J Clin Diagn Res 11:BC05–BC08

Rabiei Z (2017) Anticonvulsant effects of medicinal plants with emphasis on mechanisms of action. Asian Pac J Trop Biomed 7:166–172

Ramanathan S, Archunan G, Sivakumar M, Tamil Selvan S, Fred AL, Kumar S, Gulyas B, Padmanabhan P (2018) Theranostic applications of nanoparticles in neurodegenerative disorders. Int J Nanomedicine 13:5561–5576PubMedPubMedCentral

Rana A, Musto AE (2018) The role of inflammation in the development of epilepsy. J Neuroinflammation 15:144PubMedPubMedCentral

Reis CP, Ribeiro AJ, Neufeld RJ, Veiga F (2007) Alginate microparticles as novel carrier for oral insulin delivery. Biotechnol Bioeng 96:977–989PubMed

Rezk MM (2018) A Neuro-comparative study between single/successive thorium dose intoxication and alginate treatment. Biol Trace Elem Res 185:414–423PubMed

Samuelsson AM, Jennische E, Hansson HA, Holmang A (2006) Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning. Am J Physiol Regul Integr Comp Physiol 290:R1345–R1356PubMed

Sarei F, Dounighi NM, Zolfagharian H, Khaki P, Bidhendi SM (2013) Alginate nanoparticles as a promising adjuvant and vaccine delivery system. Indian J Pharm Sci 75:442–449PubMedPubMedCentral

Seeram NP, Lee R, Heber D (2004) Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clin Chim Acta 348:63–68

Sellimi S, Younes I, Ayed HB, Maalej H, Montero V, Rinaudo M, Dahia M, Mechichi T, Hajji M, Nasri M (2015) Structural, physicochemical and antioxidant properties of sodium alginate isolated from a Tunisian brown seaweed. Int J Biol Macromol 72:1358–1367PubMed

Shekh-Ahmad T, Lieb A, Kovac S, Gola L, Wigley CW, Abramov AY, Walker MC (2019) Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy. Redox Biol. https://doi.org/10.1016/j.redox.2019.101278 PubMedPubMedCentral

Shin EJ, Jeong JH, Bing G, Park ES, Chae JS, Yen TP, Kim WK, Wie MB, Jung BD, Kim HJ, Lee SY, Kim HC (2008) Kainate-induced mitochondrial oxidative stress contributes to hippocampal degeneration in senescence-accelerated mice. Cell Signal 20:645–658PubMed

Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191PubMed

Song B (2018) Lotus leaf-inspired design of calcium alginate particles with superhigh drug encapsulation efficiency and pH responsive release. Colloids and surfaces. B, Biointerfaces 172:464–470PubMed

Stellwagen D, Malenka RC (2006) Synaptic scaling mediated by glial TNF-alpha. Nature 440:1054–1059PubMed

Sudha K, Rao AV, Rao A (2001) Oxidative stress and antioxidants in epilepsy. Clin Chim Acta 303:19–24

Tamboli AM, Rub RA, Ghosh P, Bodhankar SL (2012) Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice. Asian Pac J Trop Biomed 2:537–542PubMedPubMedCentral

Tice RR, Andrews PW, Singh NP (1990) The single cell gel assay: a sensitive technique for evaluating intercellular differences in DNA damage and repair. Basic Life Sci 53:291–301PubMed

Tonnesen HH, Karlsen J (2002) Alginate in drug delivery systems. Drug Dev Ind Pharm 28:621–630PubMed

Tzankova V, Aluani D, Kondeva-Burdina M, Yordanov Y, Odzhakov F, Apostolov A, Yoncheva K (2017) Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity. Biomedicine & pharmacotherapy 92:569–579

Vishnoi S, Raisuddin S, Parvez S (2016) Glutamate Excitotoxicity and Oxidative Stress in Epilepsy: Modulatory Role of Melatonin. Glutamate Excitotoxicity and Oxidative Stress in Epilepsy: Modulatory Role of Melatonin J Environ Pathol Toxicol Oncol 35:365–374PubMed

Weickenmeier J, de Rooij R, Budday S, Steinmann P, Ovaert TC, Kuhl E (2016) Brain stiffness increases with myelin content. Acta Biomater 42:265–272PubMed

Xie T, Wang WP, Mao ZF, Qu ZZ, Luan SQ, Jia LJ, Kan MC (2012) Effects of epigallocatechin-3-gallate on pentylenetetrazole-induced kindling, cognitive impairment and oxidative stress in rats. Neurosci Lett 516:237–241PubMed

Yeung RA, Kennedy RA (2019) A comparison of selected physico-chemical properties of calcium alginate fibers produced using two different types of sodium alginate. J Mech Behav Biomed Mater 90:155–164PubMed

Zhong L, Liu H, Zhang W, Liu X, Jiang B, Fei H, Sun Z (2018) Ellagic acid ameliorates learning and memory impairment in APP/PS1 transgenic mice via inhibition of beta-amyloid production and tau hyperphosphorylation. Exp Ther Med 16:4951–4958

Titel: Nanoformulated ellagic acid ameliorates pentylenetetrazol-induced experimental epileptic seizures by modulating oxidative stress, inflammatory cytokines and apoptosis in the brains of male mice
verfasst von: Mohamed A. El-Missiry
Azza I. Othman
Maher A. Amer
Mohammed Sedki
Sara M. Ali
Ibrahim M. El-Sherbiny
Publikationsdatum: 14.11.2019
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 2/2020
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-019-00502-4

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2020

Nrf2 deficiency increases oligodendrocyte loss, demyelination, neuroinflammation and axonal damage in an MS animal model

IFNG/IFNG-AS1 expression level balance: implications for autism spectrum disorder

Nuclear prelamin a recognition factor and iron dysregulation in multiple sclerosis

Knockdown of IL-32 protects PC12 cells against oxygen-glucose deprivation/reoxygenation-induced injury via activation of Nrf2/NF-κB pathway

Protective effects of Chrysin against memory impairment, cerebral hyperemia and oxidative stress after cerebral hypoperfusion and reperfusion in rats