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Medicinal evaluation and molecular docking study of osajin as an anti-inflammatory, antioxidant, and antiapoptotic agent against sepsis-associated acute kidney injury in rats      
Yazarlar
Mohammad Alhılal
Mardin Artuklu Üniversitesi, Türkiye
Doç. Dr. Hüseyin Serkan EROL
Kastamonu Üniversitesi, Türkiye
Serkan Yıldırım
Atatürk Üniversitesi, Türkiye
Ahmet Çakır
Kilis 7 Aralık Üniversitesi, Türkiye
Murat Koç
Ankara Yıldırım Beyazıt Üniversitesi, Türkiye
Suzan Alhılal
Türkiye
Esra Dereli
Türkiye
Ömer Alkanoğlu
Volkan Ay
İsmail Can
Kafkas Üniversitesi, Türkiye
Mesut Bünyami Halıcı
Atatürk Üniversitesi, Türkiye
Özet
Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats via the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (p < 0.001) increased lipid peroxidation (LPO) levels and significantly (p < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (p < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found via a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.
Anahtar Kelimeler
Apoptosis | inflammation | osajin | oxidative stress | SA-AKI
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı RENAL FAILURE
Dergi ISSN 0886-022X
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q1
Makale Dili Türkçe
Basım Tarihi 12-2024
Cilt No 46
Sayı 2
Doi Numarası 10.1080/0886022X.2024.2379008
Makale Linki http://dx.doi.org/10.1080/0886022x.2024.2379008