Neuroprotective effect of astaxanthin (ATX) against cognitive impairment on PTZ-induced epileptic seizures in rats and against PTZ-induced neurotoxicity in SH-SY5Y human neuroblastoma cell culture

Mustafa Karademir; Erkan Gümüş; Yaşar Taştemur; Merve Ergül; Mustafa Ergül; Sebahattin Karabulut; Recep Akkaya; Birnur Akkaya; Ahmet Şevki Taşkıran

doi:10.7197/223.vi.535637

EN TR

Neuroprotective effect of astaxanthin (ATX) against cognitive impairment on PTZ-induced epileptic seizures in rats and against PTZ-induced neurotoxicity in SH-SY5Y human neuroblastoma cell culture

Abstract

Objective: Epilepsy is a common brain disorder that seizures could cause neuronal loss in the hippocampus. Oxidative stress has an important role in the pathology of this way. The aim of this study was to investigate the neuroprotective effect of astaxanthin (ATX), on pentylenetetrazole (PTZ) induced epileptic seizures in rats and in SH-SY5Y human neuroblastoma cell culture.

Method: In our study, we used 42 male 230-250 g Wistar Albino rats. Animals were divided into seven groups as control, saline (PTZ; 1 ml/kg serum physiologic), positive control (2,5 mg/kg diazepam), 10 mg/kg, 20 mg/kg, 40 mg/kg and 80 mg/kg ATX for seven days. Thirty min after the administration of the last drug at the indicated doses, PTZ was administered 45 mg/kg to induce an epileptic seizure. The animals were observed for 30 min. Seizure stages according to the Racine Scale (RC) and first myoclonic jerk times (FMJ). Twenty four hours after PTZ injection, passive avoidance test was performed, and then brain tissues were removed for biochemical and histopathological evaluation. The hippocampal Cornu Ammonis 1 (CA1), CA3 and dentate gyrus (DG) regions were evaluated histopathologically regarding neuronal damage. Besides, oxidative stress markers total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) were measured in brain tissues. Furthermore, ATX was performed in vitro SH-SY5Y human neuroblastoma cell culture to evaluate PTZ-induced neurotoxicity.

Results: When epileptic behaviors were evaluated, ATX did not affect RC and FMJ (p>0, 05). However, ATX reduced both cognitive impairment in passive avoidance test and neuronal damage in the hippocampus (p<0, 05). Moreover, ATX reduced both TOS levels and OSI in the brain (p<0, 05). Besides of these in vitro studies, ATX increased neuronal viability in vitro.

Conclusions: Although ATX does not have antiepileptic properties directly, it has a protective effect on not only in vivo but also in vitro. These effects may occur by possible oxidative pathways.

Keywords

Astaxanthin,Neuroprotective,Cognitive impairment,PTZ induced epileptic seizures

Astaksantin’in (ATX) ratlarda oluşturulan PTZ ile indüklenmiş epileptik nöbetlerde oluşan bilişsel bozukluğa karşı ve insan SH-SY5Y nöroblastoma hücre kültüründe PTZ ile indüklenen nörotoksisiteye karşı nöroprotektif etkisi

Öz

Amaç: Epilepsi, nöbet sonrası hipokampusta nöronal kayba neden olduğu bilinen yaygın bir beyin hastalığıdır. Oksidatif stres bu patolojide önemli bir yere sahiptir. Bu çalışmanın amacı, astaksantinin (ATX), ratlarda pentilenetrazol (PTZ) ile indüklenen epileptik nöbetlerde nöroprotektif etkisininin araştırılması ve ATX ’in SH-SY5Y insan nöroblastoma hücre kültüründe PTZ ile indüklenen nörotoksisite üzerine etkisini araştırmaktır.

Yöntem: Çalışmamızda 42 adet 230-250 gr Wistar Albino cinsi erkek rat kullandık. Hayvanlar kontrol, salin (PTZ; 1 ml / kg serum fizyolojik), pozitif kontrol (2,5 mg / kg diazepam), 7 gün boyunca 10 mg / kg, 20 mg / kg, 40 mg / kg ve 80 mg ATX verilen olarak yedi gruba ayrıldı. Son ilacın belirtilen dozlarda uygulanmasından otuz dakika sonra, epileptik nöbeti indüklemek için PTZ 45 mg / kg uygulandı. Hayvanlar 30 dakika gözlendi. Racine Scale (RC) ve ilk miyoklonik jerk zamanlarına (FMJ) göre nöbet aşamaları kayıt edildi. Ratlara PTZ enjeksiyonundan yirmi dört saat sonra pasif kaçınma testi yapıldı ve daha sonra biyokimyasal ve histopatolojik değerlendirme için beyin dokuları çıkarıldı. Hipokampal Cornu Ammonis 1 (CA1), CA3 ve dentat girus (DG) bölgeleri, nöronal hasar açısından histopatolojik olarak değerlendirildi. Ayrıca, beyin dokularında oksidatif stres belirteçleri total antioksidan status (TAS), total oksidan status (TOS) ve oksidatif stres indeksi (OSI)) ölçüldü. Ayrıca ATX’ in PTZ'nin neden olduğu nörotoksisiteye olan etkisini değerlendirmek için in vitro SH-SY5Y insan nöroblastoma hücre kültürü gerçekleştirildi.

Bulgular: Epileptik davranışlar değerlendirildiğinde, ATX, RC ve FMJ'yi etkilememiştir (p> 0, 05). Bununla birlikte, ATX hem pasif kaçınma testinde bilişsel bozulmayı hem de hipokampüsteki nöronal hasarı azaltmıştır (p <0, 05). Ayrıca, ATX beyindeki hem TOS düzeylerini hem de OSI'yi düşürmüştür (p <0, 05). İn vitro SH-SY5Y insan nöroblastoma hücre kültüründe ATX’ in in vitro nöronal canlılığı arttırdığı tesbit edildi.

Sonuç: Her ne kadar ATX doğrudan antiepileptik özelliklere sahip olmasa da, sadece in vivo olarak değil in vitro olarak da nöroprotektif bir etkiye sahiptir. Bu etkilerin olası oksidatif yolaklarla oluşabileceği düşünülmektedir.

Anahtar Kelimeler

Astaksantin,Nöroprotektif etki,Bilişsel bozukluk,Epileptik Nöbetler,SH-SY5Y kültürü

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Details

Primary Language

English

Subjects

Health Care Administration

Journal Section

Research Article

Authors

Mustafa Karademir ^*
0000-0002-0734-9040
Türkiye

Yaşar Taştemur

Birnur Akkaya

Publication Date

March 28, 2019

Submission Date

March 5, 2019

Acceptance Date

March 26, 2019

Published in Issue

Year 2019 Volume: 41 Number: 1

DOI

https://doi.org/10.7197/223.vi.535637

IZ

https://izlik.org/JA64LG25CK

Cite

RIS / Bibtex

AMA

1.Karademir M, Gümüş E, Taştemur Y, et al. Neuroprotective effect of astaxanthin (ATX) against cognitive impairment on PTZ-induced epileptic seizures in rats and against PTZ-induced neurotoxicity in SH-SY5Y human neuroblastoma cell culture. CMJ. 2019;41(1):212-222. doi:10.7197/223.vi.535637

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