İn Vitro Parkinson Modelinde Melatonin Metabolitlerinden 6- Hidroksi Melatoninin Koruyucu ve Tedavi Edici Etkisinin Araştırılması

Abstract

Amaç: Parkinson hastalığı (PH) beyindeki substantia nigra bölgesinde dopaminerjik nöronların kaybıyla birlikte bradikinezi, kas sertliği, bozulmuş duruş-yürüyüş, hipokinetik hareket bozukluğu ve istirahat tremoru ile karakterize nörodejeneratif bir hastalıktır. PH tedavisi, motor semptomları hafifletmeyi amaçlayan ancak zamanla önemli yan etkilere yol açan semptomatik tedavilerle sınırlıdır. Bu nedenle, semptomatik tedavilere alternatif olarak yeni tedavi yaklaşımlarına ihtiyaç duyulmaktadır. Melatonin, geniş kapsamlı düzenleyici özelliklerinin yanı sıra nöroprotektif rolü sayesinde, geleneksel tedavi yöntemlerine ek olarak PH tedavisinde umut verici bir alternatif oluşturmaktadır. Bu çalışmada, bir melatonin metaboliti olan 6-hidroksi melatonin’in (6-OHM) in vitro Parkinson modelinde koruyucu ve tedavi edici etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: Glioblastoma (U-118MG) hücre hattında 6-hidroksi dopamin (6-OHDA) ile in vitro PH modeli oluşturulmuştur. 6-OHM’nin koruyucu etkilerini araştırmak için 50 μM konsantrasyonda 6-OHDA uygulanmasından 4 saat önce ve 6-OHM’nin tedavi edici etkilerini araştırmak için ise 6-OHDA uygulanmasından 4 saat sonra 3 farklı konsantrasyonlarda (7nM, 8nM, 9nM) 6-OHM uygulanmıştır. Hücre canlılığı XTT (2,3‐bis [2-metoksi-4-nitro–5‐sulfofenil] 2H-tetrazolyum-5-karboksianilid tuzu) testi kullanılarak ölçülmüştür. Bulgular: 6-OHM, tek başına uygulandığında hücre hattında toksik bir etki göstermemiştir. 6-OHM, U-118 MG hücre hattında 6-OHDA ile oluşturulan in vitro PH modelinde hem koruyucu hem de tedavi edici etki göstermiştir. Bulgularımıza göre 7 nM, 8 nM ve 9 nM konsantrasyonları sırasıyla hücre canlılığını sırasıyla %18,2, %17,8, %17,3 arttırarak koruyucu etki, sırasıyla %6,7, %6,2 ve %5 arttırarak tedavi edici etki göstermiştir. Sonuç: Bu deneysel çalışma 6-OHM’nin tek başına veya güncel olarak kullanılan Parkinson ilaçlarıyla birlikte, deney hayvanları ve klinik çalışmalar sonrasında PH’ye karşı koruyucu ve terapötik bir ajan olarak geliştirilebileceğini göstermektedir.

Keywords

• Parkinson Hastalığı
• oskidatif stres
• melatonin
• nörodejeneratif hastalıklar

Investigation of Protective and Therapeutic Effects of 6-Hydroxy Melatonin, a Melatonin Metabolite, in an In Vitro Parkinson's Model

Abstract

Aim: Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra, presenting with bradykinesia, muscle rigidity, impaired posture-gait, hypokinetic movement disorders, and resting tremor. PD treatment is limited to symptomatic therapies that alleviate motor symptoms but cause significant side effects over time. Therefore, new therapeutic approaches are needed as alternatives to symptomatic treatments. Melatonin, with its broad regulatory properties and neuroprotective role, offers a promising alternative in PD treatment alongside conventional methods. This study aimed to investigate the protective and therapeutic effects of 6-hydroxymelatonin (6-OHM), a melatonin metabolite, in an in vitro Parkinson's model. Material and methods: An in vitro PD model was established using 6-hydroxydopamine (6-OHDA) in glioblastoma (U-118MG) cell line. To investigate 6-OHM's protective effects, 6-OHM was applied at three concentrations (7 nM, 8 nM, 9 nM) 4 hours before 50 μM 6-OHDA treatment. For therapeutic effects, 6-OHM was applied 4 hours after 6-OHDA treatment. Cell viability was measured using XTT assay. Results: 6-OHM showed no toxic effects when applied alone. 6-OHM demonstrated both protective and therapeutic effects in the 6-OHDA-induced in vitro PD model. The 7 nM, 8 nM, and 9 nM concentrations increased cell viability by 18.2%, 17.8%, and 17.3% respectively for protective effects, and by 6.7%, 6.2%, and 5% respectively for therapeutic effects. Conclusion: This experimental study demonstrates that 6-OHM could be developed as a protective and therapeutic agent against PD, either alone or combined with current Parkinson's medications, following animal and clinical studies.

Keywords

• Parkinson
• Oxidative stress
• 6-Hydroxy melatonin
• Melatonin metabolite

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