Turkiye Klinikleri Journal of Veterinary Sciences

.: ORIGINAL RESEARCH
Effects of Oleuropein on Nitric Oxide, Glutathione, Malondialdehyde Levels and Glutathione Peroxidase Activities in Various Tissues of Streptozotocin-Induced Diabetic Rats Treated with Metformin and Insulin
Streptozotosin ile Diyabet Oluşturulmuş ve Metformin ile İnsülin Uygulanan Ratlarda Oleuropein'in Çeşitli Dokularda Nitrik Oksit, Glutatyon, Malondialdehit Düzeyleri ve Glutatyon Peroksidaz Aktivitesi Üzerine Etkileri
Nadide Nabil KAMİLOĞLUa, Barış YILDIZa, Oğuz MERHANb, Metin ÖĞÜNb, Aysel GÜVENc, Ekin Emre ERKILIÇd, Tarık MECİTa, Pelin ŞAHİNa, Hülya HASTÜRKa
Departments of
aPhysiology,
bBiochemistry,
dInternal Medicine, Kafkas University Faculty of Veterinary Medicine, Kars, TURKEY
cBaşkent University Vocational School of Health, Ankara, TURKEY
Turkiye Klinikleri J Vet Sci. 2019;10(1):1-10
doi: 10.5336/vetsci.2018-63762
Article Language: EN
Full Text
ABSTRACT
 Objective: The aim of the present study was to investigate the effects of oleuropein on nitric oxide (NO) and oxidant-antioxidant levels in tissues of streptozotocin-induced diabetic rats treated with metformin and insulin. Material and Methods: A total of 40 male Sprague-Dawley rats were used in this study. Animals were divided into 5 groups (n=8) including 3 experiment and 2 control groups. Saline solution was injected intraperitoneally (IP) to the rats in control group. 50 mg/kg STZ was given IP to the Diabetic Control, 50 mg/kg streptozotocin (STZ)+100 mg/kg Metformin+4 IU/kg insulin was given IP to Group 1, 50 mg/kg STZ+100 mg/kg Metformin+4 IU/kg insulin was given IP and 30 mg/kg oleuropein was given orally to Group 2 and 50 mg/kg STZ IP and 30 mg/kg oleuropein was given orally to Group 3. Results: Metformin and insulin with oleuropein have a synergistic effect on regulatory activity of the GSH, MDA, NO levels and GSHPx activities of the kidney, brain and heart tissues. Using metformin and insulin with oleuropein increased the GSH levels of the kidney (p<0.001), brain (p<0.001) and heart tissues (p<0.05); also increased the GSHPx activity of the brain (p<0.01) and the heart tissues (p<0.001) and reduced MDA and NO levels of the kidney, brain and heart tissues (p<0.001). There were no statistically significant differences in GSHPx activity of kidney tissues of experimental groups. Conclusion: Using oleuropein, on streptozotocin-diabetics, in combination with metformin and insulin seems to have synergistic effect on the antioxidants in kidney, brain and heart tissues and effective in regulating the NO level on tissues.

Keywords: Deneysel diabetes mellitus; glutatyon; glutatyon peroksidaz; insulin; malondialdehid; metformin; nitrik oksid; oleuropein
ÖZET
 Amaç: Bu çalışmada, streptozotosin ile diyabet oluşturulmuş ve metformin ve insülin tedavisi gören ratlarda, oleuropein'in dokularda nitrik oksit (NO) ve oksidan-antioksidan düzeyleri üzerine etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: Çalışmada, 40 Sprague-Dawley cinsi erkek rat 3 deney ve 2 kontrol olmak üzere, 5 gruba ayrıldı (n=8). Kontrol grubuna intraperitoneal (IP) olarak izotonik sodyum klorür çözeltisi uygulandı. Diyabetik Kontrol Grubu'na IP olarak 50 mg/kg STZ, Grup 1'e IP olarak 50 mg/kg Streptozotosin (STZ)+100 mg/kg Metformin+4 IU/kg insülin, Grup 2'ye IP olarak 50 mg/kg STZ+100 mg/kg Metformin+4 IU/kg insülin ve oral olarak 30 mg/kg oleuropein ve Grup 3'e IP olarak 50 mg/kg STZ ve oral olarak 30 mg/kg oleuropein verildi. Bulgular: Oleuropein ile birlikte metformin ve insülin kullanımının, böbrek, beyin ve kalp dokularının glutatyon (GSH), malondialdehit (MDA) ve NO düzeylerinin ve GSHPx aktivitelerinin düzenlenmesinde sinerjik bir etkiye sahip olduğu belirlendi. Oleuropein ile birlikte metformin ve insülin uygulanmasının böbrek (p<0,001), beyin (p<0,001) ve kalp dokusu (p<0,05) GSH düzeyleri ile beyin (p<0,01) ve kalp dokusu (p<0,001) GSHPx aktivitelerini arttırırken, böbrek, beyin ve kalp dokularında (p<0,001) MDA ve NO seviyelerini azalttığı belirlendi. Grupların, böbrek dokusu glutatyon peroksidaz (GPHPx) aktivitelerinde ise istatistiksel bir farklılığa rastlanmadı. Sonuç: Elde ettiğimiz veriler, streptozotosin ile diyabet oluşturulmuş ratlarda insülin ve metformin ile birlikte oleuropein uygulanmasının böbrek, beyin ve kalp dokularında antioksidan denge ve NO düzeyleri üzerinde düzenleyici aktivite gösterdiğini ortaya koymaktadır.

Anahtar Kelimeler: Experimental diabetes mellitus; glutathione; glutathione peroxidase; insulin; malondialdehyde; metformin; nitric oxide; oleuropein
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