Department of Medical Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Duzce University, Duzce, Turkey.
Life Sci. 2020 Sep 1;256:118016. doi: 10.1016/j.lfs.2020.118016. Epub 2020 Jun 27.
Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway.
The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 μg/kg, i.p.).
The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-α, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury.
The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.
缺血/再灌注（I/R）是急性肾损伤（AKI）的最重要原因之一，AKI 是一种以肾功能障碍和高死亡率为特征的临床综合征。需要定义新的诊断生物标志物，以更好地阐明 AKI 的病理生理学。我们首次旨在研究姜黄素的保护作用，姜黄素具有抗氧化和抗炎特性，并且是 12/15 脂氧合酶抑制剂 LOXblock-1，通过调节炎症过程、氧化应激、细胞凋亡和 semaphorin-plexin 通路来抑制 I/R 诱导的 AKI。
将大鼠分为五组，每组 8 只：假手术组、I/R 组、I/R+DMSO（1%，腹腔内注射）组、I/R+姜黄素（100mg/kg，腹腔内注射）组、I/R+LOXblock-1（2μg/kg，腹腔内注射）组。
I/R 组血清中肾功能生物标志物（BUN、CREA 和 UA）显著升高。通过 ELISA 测量的炎症（TNF-α、IL-6 和 MCP-1）、细胞凋亡（CYCS 和 CASP3）和氧化应激参数（MDA、MPO、TAS 和 TOS）在 I/R 组中显著增加。在组织病理学分析中，观察到 I/R 导致肾脏组织严重损伤。发现 SEMA3A 在 I/R 组中血清水平和 mRNA 表达均增加。通过测量和组织病理学分析观察到，姜黄素和 LOXblock-1 通过 semaphorin-plexin 通路减少炎症反应、氧化应激和细胞凋亡。姜黄素通过其抗氧化特性在 I/R 损伤中比 LOXblock-1 更有效。
本研究通过抑制 SEMA3A 作为一种新的生物标志物，揭示了姜黄素和 LOXblock-1 对急性肾损伤的保护作用。
