YÜKSEK YAĞLI DİYET / STREPTOZOTOSİN İLE İNDÜKLENEN DİYABETİK FARELERDE METFORMİNİN HEPATORENAL HASARA KARŞI KORUYUCU ETKİLERİ

Year 2022, , 244 - 251, 18.07.2022

Songül Doğanay , Özcan Budak , Nurten Bahtiyar , Veysel Toprak

https://doi.org/10.18229/kocatepetip.840797

Abstract

AMAÇ: Sunulan bu çalışmada yüksek yağlı diyet ve streptozotosin ile deneysel tip 2 diyabet oluşturulan farelerde metformin tedavisinin karaciğer ve böbrek dokularında antioksidan etkisinin araştırılması amaçlandı.
GEREÇ VE YÖNTEM: Yirmi bir adet yetişkin (11-12 haftalık 15-18 g) C57BL6 erkek fare rastgele üç gruba ayrıldı; Kontrol grubu (K), Diyabet grubu (D), ve Diyabet+Metformin tedavi grubu (D+MTF). D ve D+MTF grupları 4 hafta süreyle yağ oranı %60 olan yüksek yağlı diyetle beslendi. 4. Haftanın sonunda 30 mg/kg tek doz streptozotosin intraperitoneal uygulanarak tip 2 diyabet oluşturuldu. Metformin 300 mg/kg/gün dozunda gavaj ile verildi. Deney sonunda alınan karaciğer ve böbrek örneklerinde; glutatyon (GSH), katalaz (KAT) ve malondialdehit (MDA) düzeyleri spektrofotometrik yöntemle ölçüldü. Hemotoksilen ve Eozin ile boyanan doku kesitleri histomorfolojik olarak değerlendirildi.
BULGULAR: Çalışma sonuçları diyabetik hayvanların karaciğer ve böbrek dokularında MDA düzeylerinin arttığını gösterdi. Metformin tedavisinin her iki dokuda da MDA düzeylerini azaltıp, GSH ve KAT düzeylerini artırdığı ancak bu artışın karaciğerde anlamlı düzeyde olmadığı (p>0,05), böbrekte ise anlamlı düzeyde olduğu bulundu (p<0,05). Ayrıca Histopatolojik değerlendirme sonuçlarında D+MTF grubunda nadir alanlarda vakuolizasyon, yer yer nekroz ve sinozoidal tıkanıklık görülürken, D grubu karaciğerlerinde yoğun vakuolizasyon, yüksek oranda sinozoidal tıkanıklık ve nekroz görüldü. Böbrek dokusunda K grubunda tübüler yapının normal yapıda olduğu; D grubunda, tübüllerin genişlediği ve yoğun kanama alanlarının olduğu; D+MTF grubunda ise nadir alanlarda tübül yapılarında vakuollerin olduğu görüldü.
SONUÇ: Bu çalışmanın sonuçları, Diyabette dokularda oksidatif stresin oluştuğunu, metformin tedavisinin diyabette artan oksidatif stres üzerinde düzeltici etki göstererek dokularda hasar oluşmasını engellediğini göstermektedir.

Keywords

Gulutatyon, Metformin, Oksidatif stres, Tip 2 diyabet.

PROTECTIVE EFFECTS OF METFORMIN AGAINST HEPATORENAL INJURY IN HIGH-FAT DIET/STREPTOZOTOCINE-INDUCED DIABETIC MICE

Abstract

OBJECTIVE: In this study, it was aimed to investigate the antioxidant effect of metformin treatment on liver and kidney tissues in mice with experimental type 2 diabetes induced by a high-fat diet and streptozotocin.
MATERIAL AND METHODS: Twenty-one adult C57BL6 male mice were randomly divided into three groups as Control group (C), Diabetes group (D), and Diabetes + Metformin group (D + MTF). Groups D and D + MTF were fed a high-fat diet with 60% fat for four weeks. After the 4th week, 30 mg/kg streptozotocin was applied intraperitoneally, and type 2 diabetes was induced. 300 mg/kg/day Metformin was given by gavage. Glutathione (GSH), catalase (CAT) and malondialdehyde (MDA) levels in liver and kidney samples were measured by spectrophotometric method. Tissue sections were stained with Hematoxylin and Eosin and evaluated histomorphologically.
RESULTS: The results showed that MDA levels increased in the liver and kidney tissues of diabetic animals. It was found that MTF treatment decreased MDA levels in both tissues and increased GSH and CAT levels, but this increase was not significant in the liver (p> 0.05), while it was significant in the kidney (p <0.05). In addition, in the histopathological evaluation results, vacuolization, occasional necrosis and synozoid occlusion were observed in rare areas in the D+MTF group, while intense vacuolization, high rates of synozoidal occlusion and necrosis were observed in group D livers. In kidney tissue, the tubular structure in the group C was normal while the tubules were enlarged in group D, and there were dense bleeding areas. In the D+MTF group, vacuoles were observed in the tubule structures in rare areas.
CONCLUSIONS: The results of this study show that oxidative stress occurs in tissues in diabetes and that metformin treatment prevents tissue damage by showing a corrective effect on the increased oxidative stress in diabetes.

Keywords

Glutathione, Metformin, Oxidative stress, Type 2 diabetes.

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