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 |