Streptozotosin ile deneysel diyabet oluşturulmuş sıçanlarda silibinin'in antidiyabetik ve endotel disfonksiyonu üzerine etkileri
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Tarih
2023
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Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/embargoedAccess
Özet
Diabetes mellitus (DM), insülin sekresyonunda ve/veya etkisinde görülen azalma sonucu ortaya çıkan hiperglisemi ile karakterize kronik metabolik bir hastalıktır. DM tedavisindeki ilerlemelere rağmen, terapötik hedeflere ulaşmak her zaman mümkün olmamaktadır. Bu durum hastaların DM tedavisine ek olarak "tamamlayıcı" tıbbi alternatiflere yönelmesine yol açmaktadır. Bitkisel tıbbi ürünleri içeren takviye gıdalar sağlıklı ve DM'li bireyler tarafından yaygın şekilde kullanılmaktadır. Bu çalışmada sağlıklı ve streptozotosin (STZ) ile deneysel tip I diyabet (T1DM) oluşturulan sıçanlarda Silybum marianum bitkisinin aktif bileşenlerden olan silibinin'in antidiyabetik ve endotel disfonksiyonu üzerine etkileri araştırılmıştır. Çalışmada 48 adet 350-440 g ağırlığında Wistar albino cinsi erkek sıçan kullanılmıştır. Sıçanlar sağlıklı kontrol (SK), diyabet kontrol (DMK), SLB30 (silibinin 30 mg/kg), SLB60 (silibinin 60 mg/kg), DM+SLB30 (diyabet + silibinin 30 mg/kg), DM+SLB60 (diyabet + silibinin 60 mg/kg) olmak üzere 6 gruba ayrılmıştır. Deneysel T1DM modeli oluşturmak için DMK, DM+SLB30, DM+SLB60 gruplarına tek doz 50 mg/kg STZ uygulanmı ve STZ uygulamasından 72 saat sonra diyabet modeli doğrulanmıştır. SLB30, SLB60, DM+SLB30, DM+SLB60 grubu sıçanlara 8 hafta boyunca silibinin uygulaması 30 mg/kg ve 60 mg/kg olmak üzere iki farklı dozda gerçekleştirilmiştir. İki haftada bir kan glikoz düzeyi ve canlı ağırlık ölçümleri yapılmıştır. Sıçanlardan 8. haftanın sonunda anestezi altında aort, pankreas dokuları ve kan örnekleri alınmıştır. Torasik aort dokularında qRT-PCR ile VCAM-1 ve eNOS gen ekspresyon ölçümlerinin yanı sıra in vitro izole organ banyosunda asetilkoline bağlı gevşeme yanıtları incelenmiştir. Pankreas dokuları sıçan insülin antikoru kullanarak immunohistokimyasal olarak incelenmiştir. Alınan kan örneklerinden HbA1c ve insülin düzeyi ölçümü yapılmıştır. Silibinin tedavisi STZ ile T1DM oluşturulan sıçanlarda gelişen hiperglisemiyi ve HbA1c düzeylerini azaltmış, kandaki insülin seviyelerini ise artırmıştır. Bunun yanında, silibinin tedavisi alan T1DM'li sıçanların DMK'ya göre pankreas dokularında insülin antikoruyla boyanma şiddeti ve yaygınlığı artmıştır. Ayrıca silibinin eNOS ekspresyonunu arttırmış ve VCAM-1 ekspresyonunu azaltmıştır. eNOS ekspresyonundaki artışla paralel olarak asetilkolin, T1DM'li silibinin tedavi gruplarının aort dokularında DMK'ya göre daha fazla gevşeme oluşturmuştur. Çalışmada yüksek dozda silibinin tedavisi alan sağlıklı sıçanların eNOS ekspresyonlarında artış görülmüştür. Sonuç olarak bu çalışmadan elde ettiğimiz bulgular silibinin tedavisinin T1DM'de gelişen hiperglisemi, hipoinsülinemi, ağırlık kaybı ve pankreas hasarını iyileştirebileceğini ayrıca eNOS ekspresyonlarını artırarak hem sağlıklı hem T1DM'de endotel disfonksiyon üzerine koruyucu olabileceğini göstermektedir.
Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia and results from impaired insulin secretion, insulin action, or both. In spite of progress in the treatment of DM, it's not at all time possible to achieve therapeutic goals. This situation leads patients to turn to "complementary" medical alternatives in addition to DM treatment. Supplementary foods containing herbal medicinal products are widely used by healthy individuals and individuals with DM. In this study, the effects of silibinin, one of the active components of the Silybum marianum plant, on antidiabetic and endothelial dysfunction in healthy and streptozotocin (STZ)-induced experimental type I diabetes (T1DM) rats were investigated. In this study, 48 male Wistar albino rats weighing 350-440 g were used. Rats were randomly divided into 6 groups: healthy control (SK), diabetes control (DMK), SLB30 (silibinin 30 mg/kg), SLB60 (silibinin 60 mg/kg), DM+SLB30 (diabetes + silibinin 30 mg/kg), DM+SLB60 (diabetes + silibinin 60 mg/kg). To induce experimental T1DM, a single dose of 50 mg/kg STZ was administered to the DMK, DM+SLB30, DM+SLB60 groups, and the diabetes model was confirmed 72 hours after STZ administration. Silibinin was administered to SLB30, SLB60, DM+SLB30, DM+SLB60 groups for 8 weeks at two different doses: 30 mg/kg and 60 mg/kg. Blood glucose level and body weight measurements were made every two weeks. At the end of the 8th week, aorta, pancreatic tissues and blood samples were taken from the rats under anesthesia. Besides VCAM-1 and eNOS gene expression measurements by qRT-PCR in thoracic aortic tissues, acetylcholine-induced relaxation responses in isolated organ bath in vitro were investigated. Pancreatic tissues were examined immunohistochemically using rat insulin antibodies. HbA1c and insulin levels were measured from the blood samples taken. Silibinin treatment decreased hyperglycemia and HbA1c levels, and increased insulin levels in rats with STZ-induced T1DM. In addition, the intensity and prevalence of insulin antibody staining in pancreatic tissues of rats with T1DM treated with silibinin were increased compared to DMK. In addition, silibinin increased eNOS expression and decreased VCAM-1 expression. In parallel with the increase in eNOS expression, acetylcholine caused more relaxation than DMK in the aortic tissues of silibinin treatment groups with T1DM. In the study, healthy rats treated with high doses of silibinin had increased eNOS expressions. In conclusion, our findings from this study suggest that silibinin treatment can improve hyperglycemia, hypoinsulinemia and pancreatic damage in T1DM. It also shows that by increasing eNOS expressions, it may be protective on endothelial dysfunction in both healthy and T1DM.
Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia and results from impaired insulin secretion, insulin action, or both. In spite of progress in the treatment of DM, it's not at all time possible to achieve therapeutic goals. This situation leads patients to turn to "complementary" medical alternatives in addition to DM treatment. Supplementary foods containing herbal medicinal products are widely used by healthy individuals and individuals with DM. In this study, the effects of silibinin, one of the active components of the Silybum marianum plant, on antidiabetic and endothelial dysfunction in healthy and streptozotocin (STZ)-induced experimental type I diabetes (T1DM) rats were investigated. In this study, 48 male Wistar albino rats weighing 350-440 g were used. Rats were randomly divided into 6 groups: healthy control (SK), diabetes control (DMK), SLB30 (silibinin 30 mg/kg), SLB60 (silibinin 60 mg/kg), DM+SLB30 (diabetes + silibinin 30 mg/kg), DM+SLB60 (diabetes + silibinin 60 mg/kg). To induce experimental T1DM, a single dose of 50 mg/kg STZ was administered to the DMK, DM+SLB30, DM+SLB60 groups, and the diabetes model was confirmed 72 hours after STZ administration. Silibinin was administered to SLB30, SLB60, DM+SLB30, DM+SLB60 groups for 8 weeks at two different doses: 30 mg/kg and 60 mg/kg. Blood glucose level and body weight measurements were made every two weeks. At the end of the 8th week, aorta, pancreatic tissues and blood samples were taken from the rats under anesthesia. Besides VCAM-1 and eNOS gene expression measurements by qRT-PCR in thoracic aortic tissues, acetylcholine-induced relaxation responses in isolated organ bath in vitro were investigated. Pancreatic tissues were examined immunohistochemically using rat insulin antibodies. HbA1c and insulin levels were measured from the blood samples taken. Silibinin treatment decreased hyperglycemia and HbA1c levels, and increased insulin levels in rats with STZ-induced T1DM. In addition, the intensity and prevalence of insulin antibody staining in pancreatic tissues of rats with T1DM treated with silibinin were increased compared to DMK. In addition, silibinin increased eNOS expression and decreased VCAM-1 expression. In parallel with the increase in eNOS expression, acetylcholine caused more relaxation than DMK in the aortic tissues of silibinin treatment groups with T1DM. In the study, healthy rats treated with high doses of silibinin had increased eNOS expressions. In conclusion, our findings from this study suggest that silibinin treatment can improve hyperglycemia, hypoinsulinemia and pancreatic damage in T1DM. It also shows that by increasing eNOS expressions, it may be protective on endothelial dysfunction in both healthy and T1DM.
Açıklama
Doktora Tezi
Anahtar Kelimeler
Silibinin, Diabetes Mellitus, Tip 1 Diyabet, Endotel Disfonksiyon, Silibinin, Diabetes Mellitus, Type 1 Diabetes, Endothelial Dysfunction
Kaynak
WoS Q Değeri
Scopus Q Değeri
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Sayı
Künye
Ün Arslan, E. (2023). Streptozotosin ile deneysel diyabet oluşturulmuş sıçanlarda silibinin'in antidiyabetik ve endotel disfonksiyonu üzerine etkileri. (Yayımlanmamış doktora tezi). Necmettin Erbakan Üniversitesi, Sağlık Bilimleri Enstitüsü Tıbbi Farmakoloji Anabilim Dalı, Konya.
