Sapmaz Tansel, Topkaraoglu Sude, Sevgin Kubra, Tekayev Muhammetnur, Guler Eray Metin, Kuras Sibel, Aktas Selman, Irkorucu Oktay
University of Health Sciences, Hamidiye Faculty of Medicine, Department of Histology and Embryology, Istanbul, Türkiye.
University of Health Sciences, Hamidiye Faculty of Medicine, Department of Histology and Embryology, Istanbul, Türkiye.
Biochem Biophys Res Commun. 2025 Sep 1;777:152315. doi: 10.1016/j.bbrc.2025.152315. Epub 2025 Jul 5.
Ischemia and reperfusion (Is-Rp) of the kidney constitutes the leading cause of acute kidney injury (AKIn). This is an evolving process that is frequently linked to the failure of several organs. The distant organ injuries such as acute liver and lung injuries are the side effects of AKIn. In the current study, bilateral renal Is-Rp was induced in rats, and the impact of curcumin and melatonin on the lung and liver was investigated. Thirty-five adult rats, aged 10-12 weeks, were randomly assigned to five groups: the Control Group (Group 1), which underwent no surgical procedure. All other groups underwent 45 min of kidney ischemia, followed by 2 h of reperfusion. Group 2 was not administered any substance. Prior to reperfusion, the following treatments were applied: Group 3 received Is-Rp combined with melatonin (MEL), Group 4 received Is-Rp with curcumin (CUR), and Group 5 received Is-Rp with both MEL and CUR. Histological analysis was performed using Hematoxylin and Eosin (H&E), Periodic Acid-Schiff (PAS), Toluidine Blue (TB), and Masson's Trichrome (TRI) staining techniques. The preparations were evaluated for changes, and severity was graded on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The scores were aggregated and presented as liver and lung injury indices for each rat. The liver tissues of the rats were assessed for leukocyte accumulation, fibrotic alterations, sinusoidal expansion, and vascular congestion. Simultaneously, the lung tissues were evaluated for alveolar collapse, intra-alveolar bleeding, mononuclear leukocyte presence within the alveoli, intravascular leukocyte accumulation, and necrotic changes. Statistically significant differences were observed among the groups in lung injury scores, liver injury scores, and mast cell counts (p < 0.000∗∗). The use of melatonin-curcumin together reduces distant organ damage caused by renal Is-Rp injury. The concurrent use of these two antioxidants exhibits a more effective therapeutic effect than their individual application.
肾脏的缺血再灌注（Is-Rp）是急性肾损伤（AKIn）的主要原因。这是一个不断发展的过程，常与多个器官功能衰竭相关。诸如急性肝损伤和肺损伤等远处器官损伤是AKIn的副作用。在本研究中，对大鼠进行双侧肾脏Is-Rp，并研究姜黄素和褪黑素对肺和肝脏的影响。35只10 - 12周龄的成年大鼠被随机分为五组：对照组（第1组），未接受任何手术操作。所有其他组均经历45分钟的肾脏缺血，随后进行2小时的再灌注。第2组未给予任何物质。在再灌注前，进行以下处理：第3组接受Is-Rp联合褪黑素（MEL），第4组接受Is-Rp联合姜黄素（CUR），第5组接受Is-Rp联合MEL和CUR。使用苏木精和伊红（H&E）、过碘酸希夫（PAS）、甲苯胺蓝（TB）和马松三色（TRI）染色技术进行组织学分析。对标本进行变化评估，并按0（无）、1（轻度）、2（中度）和3（重度）的等级对严重程度进行分级。对分数进行汇总，并作为每只大鼠肝脏和肺损伤指数呈现。评估大鼠肝脏组织中的白细胞积聚、纤维化改变、肝血窦扩张和血管充血情况。同时，评估肺组织中的肺泡塌陷、肺泡内出血、肺泡内单核白细胞存在情况、血管内白细胞积聚和坏死变化。在各组之间观察到肺损伤评分、肝损伤评分和肥大细胞计数存在统计学显著差异（p < 0.000**）。联合使用褪黑素和姜黄素可减少肾脏Is-Rp损伤引起的远处器官损伤。这两种抗氧化剂同时使用比单独使用表现出更有效的治疗效果。
