{"title":"Naringenin loaded fucoidan/polyvinylpyrrolidone nanoparticles protect against folic acid induced acute kidney injury in vitro and in vivo.","authors":"Tao Jiang, Feikai Zhu, Xintao Gao, Xiaochen Wu, Wenyong Zhu, Chuanlong Guo","doi":"10.1016/j.colsurfb.2024.114343","DOIUrl":null,"url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a common clinical problem with no effective treatment. Excessive folic acid (FA) induced kidney tubular injury is characterized by oxidative stress and inflammation, and is a common model of AKI. The excellent pharmacological activity of naringenin (NAR) makes it a potential agent for treating AKI, but its poor solubility limits its application. This study prepared NAR loaded nanoparticles (FU/PVP-NAR) using fucoidan (FU) and polyvinylpyrrolidone (PVP) as carriers, with a particle size of 23.96 ± 2.77 nm. In vitro studies showed that FU/PVP-NAR inhibited excessive FA induced proliferation inhibition, accumulation of reactive oxygen species (ROS), and disruption of mitochondrial membrane potential (MMP) of HK-2 cells. Further confirmed that FU/PVP-NAR inhibited FA induced DNA damage and Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. In vivo studies showed that excessive FA induced AKI features in mice, such as elevated serum creatinine (SCr) and blood urea nitrogen (BUN) levels, accompanied by pathological damage to kidney tissues. The above AKI characteristics induced by FA were alleviated by FU/PVP-NAR. FU/PVP-NAR also inhibited the decrease in antioxidant enzyme levels in kidney tissues induced by FA. Furthermore, in vivo mechanism studies indicated that FU/PVP-NAR inhibited the release of inflammatory factors by inhibiting DNA damage-cGAS-STING pathway. In summary, this study provided the possibility for FU/PVP-NAR as a potential candidate drug for treating FA induced AKI.</p>","PeriodicalId":279,"journal":{"name":"Colloids and Surfaces B: Biointerfaces","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Colloids and Surfaces B: Biointerfaces","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1016/j.colsurfb.2024.114343","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOPHYSICS","Score":null,"Total":0}
引用次数: 0
Abstract
Acute kidney injury (AKI) is a common clinical problem with no effective treatment. Excessive folic acid (FA) induced kidney tubular injury is characterized by oxidative stress and inflammation, and is a common model of AKI. The excellent pharmacological activity of naringenin (NAR) makes it a potential agent for treating AKI, but its poor solubility limits its application. This study prepared NAR loaded nanoparticles (FU/PVP-NAR) using fucoidan (FU) and polyvinylpyrrolidone (PVP) as carriers, with a particle size of 23.96 ± 2.77 nm. In vitro studies showed that FU/PVP-NAR inhibited excessive FA induced proliferation inhibition, accumulation of reactive oxygen species (ROS), and disruption of mitochondrial membrane potential (MMP) of HK-2 cells. Further confirmed that FU/PVP-NAR inhibited FA induced DNA damage and Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation. In vivo studies showed that excessive FA induced AKI features in mice, such as elevated serum creatinine (SCr) and blood urea nitrogen (BUN) levels, accompanied by pathological damage to kidney tissues. The above AKI characteristics induced by FA were alleviated by FU/PVP-NAR. FU/PVP-NAR also inhibited the decrease in antioxidant enzyme levels in kidney tissues induced by FA. Furthermore, in vivo mechanism studies indicated that FU/PVP-NAR inhibited the release of inflammatory factors by inhibiting DNA damage-cGAS-STING pathway. In summary, this study provided the possibility for FU/PVP-NAR as a potential candidate drug for treating FA induced AKI.
急性肾损伤(AKI)是一种常见的临床问题,目前尚无有效的治疗方法。过量叶酸(FA)诱导的肾小管损伤以氧化应激和炎症为特征,是一种常见的 AKI 模型。柚皮苷(NAR)具有出色的药理活性,是治疗 AKI 的潜在药物,但其溶解性较差,限制了其应用。本研究以褐藻糖胶(FU)和聚乙烯吡咯烷酮(PVP)为载体制备了负载柚皮苷的纳米颗粒(FU/PVP-NAR),粒径为 23.96 ± 2.77 nm。体外研究表明,FU/PVP-NAR 可抑制过量 FA 引起的 HK-2 细胞增殖抑制、活性氧(ROS)积累和线粒体膜电位(MMP)破坏。进一步证实,FU/PVP-NAR 可抑制 FA 诱导的 DNA 损伤和环 GMP-AMP 合成酶(cGAS)-干扰素基因刺激器(STING)的激活。体内研究表明,过量 FA 会诱导小鼠出现 AKI 特征,如血清肌酐(SCr)和血尿素氮(BUN)水平升高,并伴有肾组织的病理损伤。FU/PVP-NAR 可减轻 FA 诱导的上述 AKI 特征。FU/PVP-NAR 还能抑制 FA 引起的肾组织中抗氧化酶水平的下降。此外,体内机制研究表明,FU/PVP-NAR 可通过抑制 DNA 损伤-GAS-STING 通路来抑制炎症因子的释放。总之,该研究为 FU/PVP-NAR 作为治疗 FA 引起的 AKI 的潜在候选药物提供了可能。
期刊介绍:
Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields.
Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication.
The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.