Medicinal evaluation and molecular docking study of osajin as an anti-inflammatory, antioxidant, and antiapoptotic agent against sepsis-associated acute kidney injury in rats

• Published in: Renal failure Vol. 46; no. 2; p. 2379008
• Main Authors: Alhilal, Mohammad, Erol, Huseyin Serkan, Yildirim, Serkan, Cakir, Ahmet, Koc, Murat, Alhilal, Suzan, Dereli, Esra, Alkanoglu, Omer, Ay, Volkan, Can, Ismail, Halici, Mesut Bunyami
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-12-2024; Taylor & Francis Group
• Subjects: Acute Kidney Injury - drug therapy; Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Acute Kidney Injury - prevention & control; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Apoptosis; Apoptosis - drug effects; Basic Sciences Investigations; Caspase 3 - metabolism; Cell Adhesion Molecules; Disease Models, Animal; inflammation; Interleukin-33 - metabolism; Isoflavones - pharmacology; Isoflavones - therapeutic use; Kidney - pathology; Lipid Peroxidation - drug effects; Male; Molecular Docking Simulation; osajin; oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; SA-AKI; Sepsis - complications; Sepsis - drug therapy; SA-AKI; inflammation; osajin; oxidative stress; Apoptosis
• ISSN: 0886-022X; 1525-6049; 1525-6049
• DOI: 10.1080/0886022X.2024.2379008

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
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 (
 < 0.001) increased lipid peroxidation (LPO) levels and significantly (
 < 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 (
 < 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
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.