Streptozotosin ile indüklenen diyabetik sıçanlarda safranalin antidiyabetik ve endotel disfonksiyonu üzerine etkileri
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Dosyalar
Tarih
2023
Yazarlar
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Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/embargoedAccess
Özet
Diabetes Mellitus en yaygın görülen metabolik hastalıklardan biridir. Diyabet tedavisinde oral hipoglisemik ilaçlar kullanılmakta; ancak bu ilaçların radikal bir tedavi sağlamaması ve advers etkileri nedeniyle yeni ajanlar halen araştırılmaktadır. Bitkisel kaynaklar, yeni antidiyabetik ajan keşfi için önemli bir araştırma konusudur. Safran bitkisi tedavi ve aromatik amaçlarla geleneksel tıpta sıklıkla kullanılmaktadır. Safran ekstresinin antidiyabetik etkileri in vivo ve in vitro metodlarla gösterilmiştir. Ancak safranın aktif bileşenlerinden olan safranalin antidiyabetik etki potansiyeline ilişkin literatürde yeterli bilgi bulunmamaktadır. Bu tez çalışmasında safranalin antidiyabetik ve diyabetin sebep olduğu endotel hasara karşı potansiyel koruyucu etkinliği araştırılmıştır. Çalışmada 40 adet 4 aylık Wistar albino cinsi erkek sıçan; sağlıklı kontrol (SK), diyabet kontrol (DM), diyabet+safranal (0,5 mg/kg /gün), diyabet+safranal (0,75 mg/kg/gün), diyabet+safranal (1 mg/kg/gün) olarak beş gruba ayrılmıştır. SK grubu hariç 4 gruba STZ (50 mg/kg) i.p. yolla uygulanarak diyabet modeli oluşturulmuş ve sekiz hafta boyunca tedavi gruplarına safranal 0,5; 0,75 ve 1 mg/kg (i.p.) dozunda uygulanmıştır. İki haftada bir sıçanların kan glikoz düzeyi ve ağırlık ölçümleri yapılmıştır. Sekiz haftanın sonunda sakrifiye edilen sıçanların kan örneklerinde HbA1c ve insülin düzeyleri ölçülmüş, aort ve pankreas dokuları çıkarılmıştır. Pankreas dokularında immünohistokimyasal inceleme yapılmış, torasik aort dokularından alınan örneklerin bir bölümünde qRT-PCR ile VCAM-1 ve eNOS gen ekspresyonu düzeyleri, diğer bölümünde ise izole organ banyosunda gevşeme yanıtları incelenmiştir. STZ ile T1DM oluşturulan sıçanların, 3 farklı dozda safranal ile tedavisi sıçanların ağırlıklarını etkilememiş; kan glikoz ve HbA1c düzeylerini azaltmış, insülin düzeylerini ise arttırmıştır. Ayrıca safranal tedavisinin pankreas dokularında insülin antikoruyla boyanma şiddeti ve yaygınlığını arttırdığı bulunmuştur. qRT-PCR çalışmalarında safranal ile tedavi edilen sıçanların aortasında VCAM-1 protein ekspresyonunda azalma ve eNOS ekspresyonunda artış olduğu saptanmıştır. eNOS ekspresyonundaki artışa paralel olarak safranal tedavi grubu aort dokularında T1DM'li sıçan aortlarına göre asetilkolin daha fazla gevşeme oluşturmuştur. Sonuç olarak STZ ile diyabet oluşturulmuş sıçanlarda safranalin antidiyabetik etkileri ve diyabetin neden olduğu endotel disfonksiyona karşı koruyucu potansiyeli olabileceği gösterilmiştir.
Diabetes Mellitus is one of the most common metabolic disorders. Although oral hypoglycemic drugs are used in the treatment of diabetes, these drugs do not provide a radical cure and can cause adverse effects. Therefore, new agents are still being researched. Herbal sources are an important research topic for discovering new antidiabetic agents. Saffron plant is frequently used in traditional medicine for therapeutic and aromatic purposes. There are many in vivo and clinical studies showing the antidiabetic effects of saffron extract. However, there is not enough information in the literature regarding the antidiabetic effect potential of safranal, one of the active components of saffron. In this thesis, the antidiabetic and potential protective efficacy of saffron against endothelial damage caused by diabetes was investigated. In the study, 40 male 4-month-old Wistar albino rats; healthy control (SK), diabetes control (DM), diabetes+safranal (0.5 mg/kg/day), diabetes+safranal (0.75 mg/kg/day), diabetes+safranal (1 mg/kg/day) were divided into five groups. STZ (50 mg/kg) i.p. was administered to 4 groups except the healthy control group and diabetes model was created by applying this method. Safranal was administered 0.5, 0.75 and 1 mg/kg (i.p.) to the treatment groups for eight weeks. Blood glucose levels and weights of the rats were measured every two weeks. At the end of eight weeks, HbA1c and insulin levels were measured in the blood samples of sacrified rats, and the aorta and pancreas tissues were dissected. Immunohistochemical examination was performed on pancreatic tissues, and VCAM-1 and eNOS gene expression levels were examined by qRT-PCR in one part of the samples taken from thoracic aorta tissues, and relaxation responses in the isolated organ bath in the other part. Three different doses of safranal treatment did not have an effect on weight but lowered blood glucose levels depending on the dose and duration of safranal administration. Safranal reduced HbA1c levels at all treatment doses while significantly increasing insulin levels. The staining prevalence and severity of insulin antibody in pancreatic tissues increased significantly in rats treated with safranal. In isolated thoracic aortic tissues, safranal treatment reduced VCAM-1 gene expression levels compared to the DM group, while eNOS gene expression levels increased significantly. According to isolated organ bath examinations, safranal treatment significantly increased acetylcholine relaxation responses depending on the dose. In conclusion, safranal exhibited antidiabetic activity in rats induced with diabetes by STZ. The potential protective effect of safranal treatment against endothelial dysfunction caused by diabetes was also shown.
Diabetes Mellitus is one of the most common metabolic disorders. Although oral hypoglycemic drugs are used in the treatment of diabetes, these drugs do not provide a radical cure and can cause adverse effects. Therefore, new agents are still being researched. Herbal sources are an important research topic for discovering new antidiabetic agents. Saffron plant is frequently used in traditional medicine for therapeutic and aromatic purposes. There are many in vivo and clinical studies showing the antidiabetic effects of saffron extract. However, there is not enough information in the literature regarding the antidiabetic effect potential of safranal, one of the active components of saffron. In this thesis, the antidiabetic and potential protective efficacy of saffron against endothelial damage caused by diabetes was investigated. In the study, 40 male 4-month-old Wistar albino rats; healthy control (SK), diabetes control (DM), diabetes+safranal (0.5 mg/kg/day), diabetes+safranal (0.75 mg/kg/day), diabetes+safranal (1 mg/kg/day) were divided into five groups. STZ (50 mg/kg) i.p. was administered to 4 groups except the healthy control group and diabetes model was created by applying this method. Safranal was administered 0.5, 0.75 and 1 mg/kg (i.p.) to the treatment groups for eight weeks. Blood glucose levels and weights of the rats were measured every two weeks. At the end of eight weeks, HbA1c and insulin levels were measured in the blood samples of sacrified rats, and the aorta and pancreas tissues were dissected. Immunohistochemical examination was performed on pancreatic tissues, and VCAM-1 and eNOS gene expression levels were examined by qRT-PCR in one part of the samples taken from thoracic aorta tissues, and relaxation responses in the isolated organ bath in the other part. Three different doses of safranal treatment did not have an effect on weight but lowered blood glucose levels depending on the dose and duration of safranal administration. Safranal reduced HbA1c levels at all treatment doses while significantly increasing insulin levels. The staining prevalence and severity of insulin antibody in pancreatic tissues increased significantly in rats treated with safranal. In isolated thoracic aortic tissues, safranal treatment reduced VCAM-1 gene expression levels compared to the DM group, while eNOS gene expression levels increased significantly. According to isolated organ bath examinations, safranal treatment significantly increased acetylcholine relaxation responses depending on the dose. In conclusion, safranal exhibited antidiabetic activity in rats induced with diabetes by STZ. The potential protective effect of safranal treatment against endothelial dysfunction caused by diabetes was also shown.
Açıklama
Doktora Tezi
Anahtar Kelimeler
Endotel Disfonksiyon, Diyabet, Safranal, Endothelial Dysfunction, Diabetes, Safranal
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Demirci, A. (2023). Streptozotosin ile indüklenen diyabetik sıçanlarda safranalin antidiyabetik ve endotel disfonksiyonu üzerine etkileri. (Yayımlanmamış doktora tezi). Necmettin Erbakan Üniversitesi, Sağlık Bilimleri Enstitüsü Tıbbi Farmakoloji Anabilim Dalı, Konya.
