Aims

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.

Main methods

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.).

Key findings

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.

Significance

The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.

中文翻译：

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姜黄素和LOXblock-1通过抑制信号量-plexin途径改善缺血再灌注引起的炎症和急性肾损伤。

目的

缺血/再灌注（I / R）是急性肾损伤（AKI）的最重要原因之一，AKI是具有肾功能不全和高死亡率的临床综合征。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。我们首次旨在通过调节炎症过程，氧化应激，细胞凋亡和氧化应激来研究姜黄素（其抗氧化剂和抗炎特性）和12/15脂氧合酶抑制剂LOXblock-1对I / R诱导的AKI的保护作用。 semaphorin-plexin途径。

主要方法

将大鼠分为五组，每组八只动物：假，I / R，I / R + DMSO（1％，ip），I / R +姜黄素（100 mg / kg，ip），I / R + LOXblock-1（2μg/ kg，ip）。

主要发现

I / R组血清中的肾功能生物标志物（BUN，CREA和UA）显着升高。I / R组通过ELISA测定的炎症（TNF-α，IL-6和MCP-1），凋亡（CYCS和CASP3）和氧化应激参数（MDA，MPO，TAS和TOS）显着增加。在组织病理学分析中，观察到I / R对肾脏组织造成了严重损害。在I / R组中发现SEMA3A可同时提高血清水平和mRNA表达。通过测量和组织病理学分析，观察到姜黄素和LOXblock-1可以通过信号量-plexin途径减少炎症过程，氧化应激和凋亡。姜黄素在抗I / R损伤方面具有抗氧化功能，被证明比LOXblock-1更有效。

意义

目前的研究揭示了姜黄素和LOXblock-1通过抑制SEMA3A作为一种新的生物标记物对急性肾脏损伤的保护作用。