Difenhidramin’in in vitro Parkinson modelinde nöroprotektif ve terapötik etkilerinin belirlenmesi

Year 2024, Volume: 13 Issue: 3, 116 - 122

Ahmet Çağrı Ağarı , Muhammed Ali Binzet , Cansu Kara Öztabağ , İrem Kalfa , Uygar Zarif Sevinç , Akif Hakan Kurt

https://doi.org/10.47493/abantmedj.1584839

Abstract

Amaç: Parkinson hastalığı (PH), nörodejeneratif hastalıklardan biri olup dopaminerjik nöronların ilerleyici kaybı ile karakterize edilmektedir. PH’nın yaygınlığının artması nedeniyle nöroprotektif tedavilere olan ihtiyaç artmakta ve bu tedaviler hastalığın ilerlemesini yavaşlatmak amacıyla araştırılmaktadır. Difenhidramin (DFH), histamin 1 reseptör antagonisti olarak etki göstermekte ve kan-beyin bariyerini geçerek merkezi sinir sistemi üzerinde etkili olmaktadır. Çalışmamızda, 6-hidroksidopamin (6-OHDA) ile oluşturulan in vitro PH modelinde, DFH’nin nöroprotektif ve tedavi edici etkilerini değerlendirmeyi amaçladık.
Gereç ve Yöntemler: Glioblastoma (U-118MG) hücrelerinde 6-OHDA ile in vitro PH modeli oluşturuldu. 6-OHDA uygulamasından önce ve sonra 3 farklı konsantrasyonda DFH uygulandı. DFH’nin koruyucu etkisi için hücre canlılığı, XTT hücre proliferasyon testi kullanılarak incelendi. Sonuçlar, istatiksel analiz yöntemleri ile değerlendirildi.
Bulgular: Çalışmamızda, DFH’nin doz kontrollü uygulamasının, U-118MG hücre hattında 6-OHDA ile oluşturulan in vitro Parkinson modeli üzerinde hem nöroprotektif hem de terapötik etkileri olduğunu göstermiştir. Çalışmamız sonucunda elde ettiğimiz bulgulara göre; DFH’nin 1, 10 ve 100 μM konsantrasyonlarda, 6-OHDA kontrol grubuna kıyasla, hücre canlılığını önemli ölçüde artırdığı bulunmuştur. DFH’nin 1 ve 10 μM konsantrasyonları, terapötik ve nöroprotektif kullanım için önemli bir etki göstermektedir.
Sonuç: Yapılan in vitro çalışma DFH’nin, PH modellenmiş U-118MG nöronal hücrelerin canlılığını arttırarak hücreler üzerinde nöroprotektif ve tedavi edici etkilere sahip olduğunu göstermektedir. Bunun yanında, DFH’nin PH hayvan modelleri üzerindeki etkilerini değerlendirmek için in vivo çalışmalar gereklidir.

Keywords

Parkinson Hastalığı, Glioblastoma U-118 MG, Difenhidramin, 6-hidroksidopamin, Nöroprotektif ve Terapötik Etki

Investigation of the protective and therapeutic effects of Diphenhydramine in an in vitro Parkinson’s model

Abstract

Objective: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. Due to the rising prevalence of PD, the need for neuroprotective treatments is increasing, and these are being investigated as a means to slow the disease’s progression. Diphenhydramine (DPH), acting as a histamine 1 receptor antagonist, crosses the blood-brain barrier and exerts effects on the central nervous system. Our aim in this study is to evaluate the neuroprotective and therapeutic effects of DPH in an in vitro PD model induced by 6-hydroxydopamine (6-OHDA).
Materials and Methods: An in vitro PD model was established in Glioblastoma (U-118 MG) cells using 6-OHDA. DPH was applied at three different concentrations before and after 6-OHDA application. The protective effect of DPH was evaluated by assessing cell viability using the XTT cell proliferation assay. The results were analyzed using statistical analysis methods.
Results: Our study demonstrated that dose-controlled administration of DPH has both neuroprotective and therapeutic effects on an in vitro Parkinson’s model established with 6-OHDA in the U-118MG cell line. According to our findings, DPH at concentrations of 1, 10, and 100 µM significantly increased cell viability compared to the 6-OHDA control group. DPH at 1 and 10 µM concentrations showed important potential for therapeutic and neuroprotective use.
Conclusions: The in vitro study indicates that DPH has neuroprotective and therapeutic effects on PD-modeled U-118MG neuronal cells by increasing cell viability. Nevertheless, in vivo studies are needed to evaluate the effects of DPH on animal models of PD.

Keywords

Parkinson’s Disease, Glioblastoma U-118MG, Diphenhydramine, 6-hydroxydopamine, Neuroprotective and Therapeutic Effect

Ethical Statement

This article does not contain any studies involving animals or human participants performed by any of the authors. Cell culture was used in the study.

Supporting Institution

Supported by TÜBİTAK-2209A for Ahmet Çağrı AĞARI (Project number: 1919B012302698).

Thanks

We thank to TUBİTAK 2209-A programme for the financial support.

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