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水飞蓟素对油酸诱导的急性肾损伤的保护作用:氧化应激、炎症及细胞死亡机制研究

Protective Potential of Hispidulin Against Oleic Acid-Induced Acute Kidney Injury: Investigation of Oxidative Stress, Inflammation and Cellular Death Mechanisms.

作者信息

Avci Bahri, Uguz Handan, Palabiyik Esra, Sulumer Ayse Nurseli, Askin Hakan

机构信息

Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, Erzurum, Turkey.

出版信息

J Biochem Mol Toxicol. 2025 Sep;39(9):e70461. doi: 10.1002/jbt.70461.

DOI:10.1002/jbt.70461
PMID:40852843
Abstract

Hispidulin is a natural flavonoid extracted from many plants such as Saussurea involucrata by different methods. The present study aims to evaluate the histopathologic, antioxidant and molecular effects of hispidulin in oleic acid-induced male Spraque Dawley rats. Accordingly, rats were divided into three separate groups HC: Healthy Control Group OA: Oleic Acid Group and H + OA Group. Oxidative stress markers superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) were evaluated in kidney tissues obtained from the animals of the treatment groups. The same tissues were subjected to histopathologic examination. Moreover, gene expression levels of critical regulators of apoptosis, cellular metabolism and inflammation were examined by real-time PCR to identify the molecular structure responsible for the nephrotoxic impact of oleic acid. It was observed that oleic acid (OA) led to decrease in GSH level and an increase in MPO and MDA levels in rat kidney tissues. The levels of SOD and CAT, which are among the antioxidant system components, were found to decrease. In addition, kidney damage biomarker (Kim-1), inflammation genes (Il-6, Nf-Kß), apoptotic gene (Casp3) and gene involved in extracellular matrix renewal (Mmp2) were negatively affected by OA exposure. However, it was observed that hispidulin was able to reverse all the deregulations induced by OA administration. In conclusion, oleic acid, used as an inducer of acute kidney injury, caused tissue damage by disrupting the oxidant and antioxidant balance and dysfunction in renal tissues by increasing the levels of inflammatory mediators. Hispidulin, which we use as a renoprotective agent in acute kidney injury, may be considered as an alternative, versatile and effective technique to alleviate renal injury by inhibiting inflammation, tubular cell death and oxidative stress.

摘要

滨蓟黄素是一种通过不同方法从多种植物如天山雪莲中提取的天然黄酮类化合物。本研究旨在评估滨蓟黄素对油酸诱导的雄性斯普拉格-道利大鼠的组织病理学、抗氧化和分子效应。相应地,将大鼠分为三个独立的组:HC:健康对照组;OA:油酸组;H + OA组。对治疗组动物的肾组织中氧化应激标志物超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)、丙二醛(MDA)和髓过氧化物酶(MPO)进行了评估。对相同的组织进行了组织病理学检查。此外,通过实时PCR检测凋亡、细胞代谢和炎症关键调节因子的基因表达水平,以确定对油酸肾毒性影响负责的分子结构。观察到油酸(OA)导致大鼠肾组织中GSH水平降低,MPO和MDA水平升高。发现抗氧化系统成分中的SOD和CAT水平降低。此外,肾脏损伤生物标志物(Kim-1)、炎症基因(Il-6、Nf-Kß)、凋亡基因(Casp3)和参与细胞外基质更新的基因(Mmp2)受到OA暴露的负面影响。然而,观察到滨蓟黄素能够逆转OA给药引起的所有失调。总之,用作急性肾损伤诱导剂的油酸通过破坏氧化和抗氧化平衡以及通过增加炎症介质水平导致肾组织功能障碍,从而引起组织损伤。我们用作急性肾损伤肾保护剂的滨蓟黄素可被视为一种通过抑制炎症、肾小管细胞死亡和氧化应激来减轻肾损伤的替代、通用且有效的技术。

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