Mohammad Alhilal, Huseyin Serkan Erol, Serkan Yildirim, Ahmet Cakir, Murat Koc, Suzan Alhilal, Esra Dereli, Omer Alkanoglu, Volkan Ay, Ismail Can, Mesut Bunyami Halici
{"title":"欧沙金作为抗炎、抗氧化和抗细胞凋亡药物对败血症相关急性肾损伤大鼠的药用评价和分子对接研究","authors":"Mohammad Alhilal, Huseyin Serkan Erol, Serkan Yildirim, Ahmet Cakir, Murat Koc, Suzan Alhilal, Esra Dereli, Omer Alkanoglu, Volkan Ay, Ismail Can, Mesut Bunyami Halici","doi":"10.1080/0886022X.2024.2379008","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>via</i> 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 (<i>p</i> < 0.001) increased lipid peroxidation (LPO) levels and significantly (<i>p</i> < 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 (<i>p</i> < 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 <i>via</i> 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.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262233/pdf/","citationCount":"0","resultStr":"{\"title\":\"Medicinal evaluation and molecular docking study of osajin as an anti-inflammatory, antioxidant, and antiapoptotic agent against sepsis-associated acute kidney injury in rats.\",\"authors\":\"Mohammad Alhilal, Huseyin Serkan Erol, Serkan Yildirim, Ahmet Cakir, Murat Koc, Suzan Alhilal, Esra Dereli, Omer Alkanoglu, Volkan Ay, Ismail Can, Mesut Bunyami Halici\",\"doi\":\"10.1080/0886022X.2024.2379008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>via</i> 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 (<i>p</i> < 0.001) increased lipid peroxidation (LPO) levels and significantly (<i>p</i> < 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 (<i>p</i> < 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 <i>via</i> a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). 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引用次数: 0
摘要
尽管人们一直在努力寻找治疗败血症相关性急性肾损伤(SA-AKI)的有效药物,但 SA-AKI 患者的死亡率并没有降低。我们的研究通过靶向炎症、氧化应激和细胞凋亡,评估了异黄酮欧沙金(OSJ)对大鼠 SA-AKI 的保护作用。通过盲肠结扎和穿刺(CLP)技术诱导大鼠发生多微生物败血症。用生化方法评估了肾组织中氧化应激的标志物。使用免疫组化和免疫荧光检测方法评估了白细胞介素-33(IL-33)、8-羟基脱氧鸟苷(8-OHdG)、Caspase-3 和肾损伤分子-1(KIM-1)的表达,分别作为肾组织中炎症、DNA 损伤、细胞凋亡和 SA-AKI 的指标。通过对 OSJ 与小鼠 IL-33(PDB 代码:5VI4)结合模式的分子对接研究,CLP 技术显著(p p p p)。因此,OSJ可通过抑制IL-33/LPO/8-OHdG/caspase-3途径和改善抗氧化系统来防止SA-AKI。
Medicinal evaluation and molecular docking study of osajin as an anti-inflammatory, antioxidant, and antiapoptotic agent against sepsis-associated acute kidney injury in rats.
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.
期刊介绍:
Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.