Roziglitazonun Sıçanlarda Mitokondriyal Genom Üzerindeki Etkisinin Moleküler Yöntemlerle Araştırılması

Yıl 2023, Cilt: 15 Sayı: 1, 26 - 44, 05.09.2023

Zeliha Cansel Özmen , Muhlise Alvur , Abdulkerim Bedir , Birşen Bilgici , Rukiye Nar

Öz

Amaç: Roziglitazon, Tip II diabetes mellitus tedavisinde kullanılan tiazolidindion sınıfına ait bir ilaçtır. Bu çalışmanın amacı, farklı sıçan dokularında mtDNA4834 delesyon frekansını inceleyerek, roziglitazonun mitokondriyal DNA üzerindeki etkilerini araştırmaktır.
Gereç ve Yöntemler: Sprague-Dawley sıçanlarının karaciğer, ince bağırsak, pankreas dokusu ve lenfositlerinden genomik DNA izole edildi. Numunelerin nükleer DNA, mitokondriyal DNA ve mtDNA4834 delesyon kopya sayıları real-time qPCR ile belirlendi. Hücre başına mtDNA kopya sayıları (mtDNA/hücre) ve mtDNA4834 delesyon frekansı (delesyon frekansı (%)) hesaplandı.
Bulgular: mtDNA/hücre, roziglitazonun tüm dozlarında ince bağırsak ve pankreas dokusunda kontrol grubuna göre anlamlı derecede düşüktü (p<0.05). Roziglitazon tüm dozlarında karaciğer dokusundaki mtDNA4834 delesyon frekansı (%) kontrol grubuna göre anlamlı olarak düşük bulundu (p<0.05). Aynı zamanda kontrol grupları arasında mtDNA4834 delesyon frekansı (%) ve mtDNA/hücre açısından istatistiksel olarak anlamlı farklılık vardı (p<0.05)
Sonuç: Çalışmamızın sonuçları bize, karaciğer dokusunda mtDNA4834 delesyon sıklığının azalması nedeniyle roziglitazonun bu doku üzerinde oksidan etkisinin olmadığını düşündürdü. Ancak ince barsak ve pankreas dokularında mitokondriyal DNA kopya sayılarındaki azalma roziglitazonun oksidan etkisinden kaynaklanmış olabilir.

Anahtar Kelimeler

mtDNA4834 delesyon, mitokondriyal DNA, oksidatif stres, roziglitazon

Investigation of Effect of Rosiglitazone on the Mitochondrial Genome in Rats by Molecular Methods

Öz

Objectives: Rosiglitazone is a drug which belongs to tiazolidinedione class used in the treatment of Type II diabetes mellitus. The aim of this study was to investigate the effects of rosiglitazone on the mitochondrial DNA by examining the frequency of the mtDNA4834 deletion in the different rat tissues.
Material and Methods: Genomic DNA was extracted from liver, small intestine, pancreas tissue and lymphocytes of male Sprague-Dawley rats. Nuclear DNA, mitochondrial DNA and mtDNA4834 deletion copy numbers of the samples was determined by real-time qPCR. mtDNA copy numbers per cell (mtDNA/cell) and mtDNA4834 deletion frequency (mtDNA4834 deletion frequency (%)) were calculation.
Results: The mtDNA/cell in the tissues of small intestine and pancreas were significiantly lower than in all rosiglitazone doses compared to the control group (p<0.05). The mtDNA4834 deletion frequency (%) in the liver tissue at all doses of rosiglitazone was found to be significiantly lower than in the control group (p<0.05). At the same time, there was a significiant statistical difference in the mtDNA4834 deletion frequency (%) and mtDNA/cell between the control groups (p<0.05)
Conclusion: The results of our study made us think that rosiglitazone has no oxidant effect on this tissue due to the decrease in the frequency of mtDNA4834 deletion in liver tissue. However, the decrease in mitochondrial DNA copy numbers in the small intestine and pancreas tissues may be due to the oxidant effect of rosiglitazone.

Anahtar Kelimeler

mtDNA4834 deletion, mitochondrial DNA, oxidative stress, rosiglitazone

Kaynakça

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