Elucidating the cytogenotoxic potential of gabapentin: in vitro and in silico analysis

İbrahim Halil Kenger; Mehmet Tahir Hüsunet

doi:10.17826/cumj.1629309

EN TR

Elucidating the cytogenotoxic potential of gabapentin: in vitro and in silico analysis

Abstract

Purpose: This investigation aimed to evaluate the potential cytogenotoxic effects of gabapentin (GBP) on neuroblastoma cells (SH-SY5Y cell line) given its broad range of applications. Furthermore, the interaction between GBP and DNA polymerase beta (DNApolβ) was evaluated using in silico methods. Material and Methods: The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was used to investigate the cytotoxicity of GBP at concentrations of 1 µM, 10 µM, 100 µM and 1000 µM. The IC₅₀ value of GBP was calculated, as were the genotoxic effects of GBP at concentrations of 0.14 µM, 0.28 µM, 0.56 µM and 1.12 µM, using the Comet assay. Additionally, AutoDock 4.0 was used to predict the interaction between GBP and the DNApolβ molecule in silico. Results: GBP significantly decreased the viability of SH-SY5Y cells by 70.2 ± 3.084% and 86.8 ± 3.324% at concentrations of 1 µM and 10 µM, respectively. Concentrations of GBP (0.14 µM, 0.28 µM, 0.56 µM and 1.12 µM) were found to be statistically significant for the damaged cell index (DCI) in SH-SY5Y cells at 298.219 ± 104.66, 593.436 ± 120.16, 1216.378 ± 215.96 and 1589.733 ± 472.65, respectively. The genetic damage index (GDI) for these concentrations was found to be statistically significant at 4.150 ± 1.92, 6.568 ± 1.27, 8.216 ± 0.60 and 9.181 ± 1.16, respectively. The Gibbs free binding energy of GBP with DNApolβ was calculated as -7.35 kcal/mol. Conclusion: The results of this study indicate that GBP, used in the treatment of epilepsy and neuropathic pain, increases both cytotoxicity and genotoxicity in SH-SY5Y neuroblastoma cells. Furthermore, in silico predictions have revealed a significant interaction between GBP and DNApolβ.

Keywords

Neuroblastoma , Gabapentin , genotoxicity , cytotoxicity , SH-SY5Y cell line , in slico molecular docking

Gabapentinin sitogenotoksik potansiyelinin aydınlatılması: in vitro ve siliko analizi

Öz

Amaç: Bu araştırma, geniş uygulama alanı göz önüne alındığında, gabapentinin (GBP) nöroblastoma hücreleri (SH-SY5Y hücre hattı) üzerindeki potansiyel sitogenotoksik etkilerini değerlendirmeyi amaçlamıştır. Ayrıca, GBP ve DNA polimeraz beta (DNApolβ) arasındaki etkileşim in silico yöntemler kullanılarak değerlendirilmiştir. Gereç ve Yöntem: 3-(4,5-dimetiltiyazol-2-il)-5-(3-karboksimetoksifenil)-2-(4-sülfofenil)-2H-tetrazolyum (MTS) deneyi, 1 µM, 10 µM, 100 µM ve 1000 µM konsantrasyonlarında GBP'nin sitotoksisitesini araştırmak için kullanılmıştır. Comet deneyi kullanılarak GBP'nin IC₅₀ değeri ve 0,14 µM, 0,28 µM, 0,56 µM ve 1,12 µM konsantrasyonlarında GBP'nin genotoksik etkileri hesaplanmıştır. Ek olarak, GBP ve DNApolβ molekülü arasındaki etkileşimi in silico tahmin etmek için AutoDock 4.0 kullanılmıştır. Bulgular: GBP, SH-SY5Y hücrelerinin canlılığını 1 µM ve 10 µM konsantrasyonlarında sırasıyla %70,2 ± 3,084 ve %86,8 ± 3,324 oranında önemli ölçüde azaltmıştır. GBP konsantrasyonları (0.14 µM, 0.28 µM, 0.56 µM ve 1.12 µM) SH-SY5Y hücrelerinde hasarlı hücre indeksi (DCI) için sırasıyla 298.219 ± 104.66, 593.436 ± 120.16, 1216.378 ± 215.96 ve 1589.733 ± 472.65 değerlerinde istatistiksel olarak anlamlı bulunmuştur. Bu konsantrasyonlar için genetik hasar indeksi (GDI) sırasıyla 4.150 ± 1.92, 6.568 ± 1.27, 8.216 ± 0.60 ve 9.181 ± 1.16 olarak istatistiksel olarak anlamlı bulunmuştur. GBP'nin DNApolβ ile Gibbs serbest bağlanma enerjisi -7,35 kcal/mol olarak hesaplanmıştır. Sonuç: Bu çalışmanın sonuçları, epilepsi ve nöropatik ağrı tedavisinde kullanılan GBP'nin SH-SY5Y nöroblastoma hücrelerinde hem sitotoksisiteyi hem de genotoksisiteyi artırdığını göstermektedir. Dahası, in silico tahminler GBP'nin DNApolβ ile önemli bir etkileşim içinde olduğunu göstermiştir.

Anahtar Kelimeler

nöroblastoma , gabapentin , genotoksisite , sitotoksisite , SH-SY5Y hücre hattı , in slico moleküler yerleştirme

Kaynakça

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Ayrıntılar

Birincil Dil

İngilizce

Konular

Tıbbi Genetik (Kanser Genetiği hariç)

Bölüm

Araştırma Makalesi

Yazarlar

İbrahim Halil Kenger ^*
0000-0002-9848-954X
Türkiye

Mehmet Tahir Hüsunet
0000-0003-1424-5132
Türkiye

Yayımlanma Tarihi

30 Haziran 2025

Gönderilme Tarihi

29 Ocak 2025

Kabul Tarihi

23 Mayıs 2025

Yayımlandığı Sayı

Yıl 2025 Cilt: 50 Sayı: 2

DOI

https://doi.org/10.17826/cumj.1629309

IZ

https://izlik.org/JA56CJ89ZJ

MLA

Kenger, İbrahim Halil, ve Mehmet Tahir Hüsunet. “Elucidating the cytogenotoxic potential of gabapentin: in vitro and in silico analysis”. Cukurova Medical Journal, c. 50, sy 2, Haziran 2025, ss. 435-42, doi:10.17826/cumj.1629309.

Bu eser Creative Commons Atıf-Gayriticari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.

Elucidating the cytogenotoxic potential of gabapentin: in vitro and in silico analysis

Abstract

Keywords

Gabapentinin sitogenotoksik potansiyelinin aydınlatılması: in vitro ve siliko analizi

Öz

Anahtar Kelimeler

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

DOI

IZ

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