Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking.

IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biological Chemistry Pub Date : 2024-12-23 DOI:10.1515/hsz-2024-0068
Arif Ali, Igor Moreira de Almeida, Emanuel Paula Magalhães, Jesyka Macedo Guedes, Francisco Ferdinando Mesquita Cajazeiras, Marcia Machado Marinho, Emmanuel Silva Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Hélcio Silva Dos Santos, Geraldo Bezerra da Silva Júnior, Alice Maria Costa Martins
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Abstract

Ischemia/reperfusion injury (I/R) is a leading cause of acute kidney injury (AKI) in conditions like kidney transplants, cardiac surgeries, and nephrectomy, contributing to high global mortality and morbidity. This study aimed to analyze the protective effects of 2'-hydroxychalcones in treating I/R-induced AKI by targeting key pathological pathways. Considering strong antioxidant action along with other pharmacological roles of chalcone derivatives, six 2'-hydroxychalcones were synthesized via Claisen-Schmidt condensation and analyzed for their protective effects in an I/R induced AKI model using HK-2 cells. Among six 2'-hydroxychalcones, chalcone A4 significantly increased the HK-2 cells viability compared to I/R group. Chalcone A4 reduced the cell death events by reducing generation of cytoplasmic ROS and mitochondrial transmembrane potential. It also increased GSH and SOD activity while reducing TBARS levels, indicating strong antioxidant action. Scanning electron microscope images showed that chalcone A4 reversed I/R-induced morphological changes in HK-2 cells, including apoptotic blebbing and cytoplasmic fragmentation. Furthermore, in silico studies revealed interactions with NADPH oxidase 4, further supporting its protective role in I/R-induced AKI. These results showed that chalcone A4 possess potential protective action against I/R induced cellular damage possibly due to its strong antioxidant action and potential interaction with NOX4 subunit of NADPH oxidase.

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缺血再灌注损伤(I/R)是肾移植、心脏手术和肾切除术等情况下急性肾损伤(AKI)的主要原因,导致全球死亡率和发病率居高不下。本研究旨在分析 2'-hydroxychalcones 通过靶向关键病理通路在治疗 I/R 诱导的 AKI 中的保护作用。考虑到查耳酮衍生物具有很强的抗氧化作用和其他药理作用,研究人员通过克莱森-施密特缩合法合成了六种 2'-羟基查耳酮,并利用 HK-2 细胞分析了它们在 I/R 诱导的 AKI 模型中的保护作用。在六种 2'-羟基查尔酮中,与 I/R 组相比,查尔酮 A4 能显著提高 HK-2 细胞的存活率。查尔酮 A4 通过降低细胞质 ROS 的生成和线粒体跨膜电位,减少了细胞死亡事件。它还提高了 GSH 和 SOD 活性,同时降低了 TBARS 水平,这表明它具有很强的抗氧化作用。扫描电子显微镜图像显示,查尔酮 A4 逆转了 I/R 诱导的 HK-2 细胞形态学变化,包括细胞凋亡出血和细胞质破碎。此外,硅学研究还发现了它与 NADPH 氧化酶 4 的相互作用,进一步证实了它在 I/R 诱导的 AKI 中的保护作用。这些结果表明,查尔酮 A4 对 I/R 诱导的细胞损伤具有潜在的保护作用,这可能是由于其强大的抗氧化作用以及与 NADPH 氧化酶 NOX4 亚基的潜在相互作用。
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来源期刊
Biological Chemistry
Biological Chemistry 生物-生化与分子生物学
CiteScore
7.20
自引率
0.00%
发文量
63
审稿时长
4-8 weeks
期刊介绍: Biological Chemistry keeps you up-to-date with all new developments in the molecular life sciences. In addition to original research reports, authoritative reviews written by leading researchers in the field keep you informed about the latest advances in the molecular life sciences. Rapid, yet rigorous reviewing ensures fast access to recent research results of exceptional significance in the biological sciences. Papers are published in a "Just Accepted" format within approx.72 hours of acceptance.
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