Chandan HIRENALLURE MAHESHWARAPPA, Krishna KAMSAGARA LINGANNA, Prashanth Kumar BOMMENAHALLI REVANAPPA, Seema MEHDI, Shreyas AYACHIT, Suman SUMAN, Nandini HITTANAHALLI SHIVAKUMAR, Sneha DESAI, Swerna ESWARAN

Yeni Glitazonların, STZ ile İndüklenmiş Hiperglisemik Sıçan Modelinde Hiperglisemiyi Tersine Çevirmesi

Diabetes mellitus, insülin salgılanmasının veya insüline duyarlılığın azalması ile karakterize edilen en yaygın kronik metabolik hastalıktır. Aynı zamanda plazmada glukoz seviyelerinin yetersiz kontrolü hastalığıdır. Bu çalışmada, yeni glitazonların, STZ ile indüklenmiş hiperglisemik sıçanlardaki hipoglisemik aktiviteleri değerlendirildi. In vivo çalışmalardan önce, 32 adet yeni glitazonun moleküler yerleştirme çalışması gerçekleştirildi. Moleküler yerleştirme çalışması, C5 ve C22 bileşiklerinin hedef protein 3CS8 ile daha iyi bağlandığını gösterdi. Akut toksisite çalışmaları, OECD kılavuzu 425 kullanılarak dişi farelerde yapıldı. Bileşikler, sıçanlarda test edildiğinde 300 mg/ kg’da mortalite göstermedi. Bu nedenle in vivo çalışmalar için bu doz seçildi. C5 ve C22 bileşiklerinin hipoglisemik aktiviteleri, 10 ve 20 mg / kg konsantrasyonda, STZ ile indüklenmiş hiperglisemik sıçanlarda değerlendirildi. Her iki dozda da (10 mg hem de 20 mg/ kg) bileşik C5, C22’den daha iyi bir aktivite gösterdi, C22 daha yüksek dozda daha iyi bir aktivite sergiledi. Aktivite 0, 7, 14 ve 21. gününde davranışsal parametreler, plazma kan glukoz seviyesi ile değerlendirildi. Çalışma süresi üç hafta olup, 21. günde, hayvanlar sakrifiye edildi ve biyokimyasal analizler yapıldı. Bileşik C5, C22 ile karşılaştırıldığında önemli bir aktivite gösterdi. Yeni glitazonların hipoglisemik aktivitesini ispatlamak için daha fazla araştırma gerekmektedir.

Anahtar Kelimeler:

Moleküler yerleştirme, PPARγ, glitazonlar, diyabet, 3CS8, lipit profili.

Novel Glitazones Reverses Hyperglycemia In STZ Induced Hyperglycaemic Rat Model

Diabetes mellitus is the most common chronic metabolic disorder characterized by reduced secretion of insulin or sensitivity to the insulin. It is also a disease of inadequate control of glucose levels in the blood plasma. The present study was formulated to assess the novel glitazones for hypoglycaemic activity in STZ induced rat model. Before in-vivo studies, thirty-two virtual compounds of novel glitazones were subjected to the molecular docking study. The docking study showed that, the compounds C5 and C22 showed the better binding activity with the target protein 3CS8. The acute toxicity studies were done on female rats using OECD guideline 425. No mortality observed at 300 mg/kg per kg body weight and based on this result, the dose for in-vivo studies was chosen. The compounds C5 and C22 were evaluated for the hypoglycaemic activity at 10 and 20 mg/kg body weight in STZ induced hyperglycaemic rats. The compound C5 at both the dose (10 mg and 20 mg/kg) showed the better activity than C22, where as C22 exhibited better activity at higher dose when tested. The activity was assessed by behavioural and biochemical parameters, on 0th ,7 th, 14 th and 21st day. The study duration was three weeks, on 21st day, the animals were sacrificed and biochemical estimations were done. The compound C5 showed significant activity when compared with C22. The current findings gives a lead for further research to prove the hypoglycaemic activity of novel glitazones at molecular level by employing some more research models.

Keywords:

Molecular docking, PPARγ, glitazones, diabetes, 3CS8, lipid profile.,

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