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单次输注聚乙二醇包被的超顺磁性磁铁矿纳米颗粒对大鼠肝脏和心脏中参与铁代谢的基因表达有不同影响。

A Single Infusion of Polyethylene Glycol-Coated Superparamagnetic Magnetite Nanoparticles Alters Differently the Expressions of Genes Involved in Iron Metabolism in the Liver and Heart of Rats.

作者信息

Kluknavsky Michal, Micurova Andrea, Skratek Martin, Balis Peter, Okuliarova Monika, Manka Jan, Bernatova Iveta

机构信息

Centre of Experimental Medicine, Slovak Academy of Sciences, Institute of Normal and Pathological Physiology, 813 71 Bratislava, Slovakia.

Institute of Measurement Science, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia.

出版信息

Pharmaceutics. 2023 May 12;15(5):1475. doi: 10.3390/pharmaceutics15051475.

DOI:10.3390/pharmaceutics15051475
PMID:37242717
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10220547/
Abstract

This study investigated genotype- and tissue-related differences in the biodistribution of superparamagnetic magnetite (FeO) nanoparticles (IONs) into the heart and liver of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats after a single i.v. infusion of polyethylene glycol-coated IONs (~30 nm, 1mg Fe/kg) 100 min post-infusion. The effects of IONs on the expression of selected genes involved in the regulation of iron metabolism, including , and , and their possible regulation by nuclear factor (erythroid-derived 2)-like 2 (NRF2, encoded by ) and iron-regulatory protein (encoded by ) were investigated. In addition, superoxide and nitric oxide (NO) production were determined. Results showed reduced ION incorporations into tissues of SHR compared to WKY and in the hearts compared to the livers. IONs reduced plasma corticosterone levels and NO production in the livers of SHR. Elevated superoxide production was found only in ION-treated WKY. Results also showed differences in the regulation of iron metabolism on the gene level in the heart and liver. In the hearts, gene expressions of , , , , , , and correlated with but not with suggesting that their expression is regulated by mainly iron content. In the livers, expressions of , , , , and correlated with but not with , suggesting a predominant effect of oxidative stress and/or NO.

摘要

本研究调查了在静脉内单次输注聚乙二醇包被的超顺磁性磁铁矿（FeO）纳米颗粒（IONs，~30 nm，1mg Fe/kg）100分钟后，正常血压的Wistar Kyoto（WKY）大鼠和自发性高血压（SHR）大鼠的心脏和肝脏中，IONs生物分布的基因型和组织相关差异。研究了IONs对参与铁代谢调节的选定基因（包括 、 和 ）表达的影响，以及它们可能受核因子（红细胞衍生2）样2（由 编码的NRF2）和铁调节蛋白（由 编码）的调节。此外，还测定了超氧化物和一氧化氮（NO）的产生。结果显示，与WKY大鼠相比，SHR大鼠组织中ION的掺入减少，与肝脏相比，心脏中ION的掺入也减少。IONs降低了SHR大鼠肝脏中的血浆皮质酮水平和NO产生。仅在ION处理的WKY大鼠中发现超氧化物产生增加。结果还显示心脏和肝脏在基因水平上铁代谢调节存在差异。在心脏中， 、 、 、 、 、 、 和 的基因表达与 相关，但与 无关，表明它们的表达主要受铁含量调节。在肝脏中， 、 、 、 和 的表达与 相关，但与 无关，表明氧化应激和/或NO起主要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/36b2572d7646/pharmaceutics-15-01475-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/b1348bb0eeaf/pharmaceutics-15-01475-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/212cbd1f5a9e/pharmaceutics-15-01475-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/23ad8ad23c44/pharmaceutics-15-01475-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/d8aa29e291de/pharmaceutics-15-01475-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/ed9b4afe9dbc/pharmaceutics-15-01475-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/92fb1b4739e9/pharmaceutics-15-01475-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/36b2572d7646/pharmaceutics-15-01475-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/b1348bb0eeaf/pharmaceutics-15-01475-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/212cbd1f5a9e/pharmaceutics-15-01475-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/23ad8ad23c44/pharmaceutics-15-01475-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/d8aa29e291de/pharmaceutics-15-01475-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/ed9b4afe9dbc/pharmaceutics-15-01475-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/92fb1b4739e9/pharmaceutics-15-01475-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/10220547/36b2572d7646/pharmaceutics-15-01475-g007.jpg

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Vascular Repair by Grafting Based on Magnetic Nanoparticles.

Pharmaceutics. 2022-7-8

[2]
Pharmacokinetics of magnetic iron oxide nanoparticles for medical applications.

J Nanobiotechnology. 2022-6-27

[3]
Hemosiderin Accumulation in Liver Decreases Iron Availability in Tachycardia-Induced Porcine Congestive Heart Failure Model.

Int J Mol Sci. 2022-1-18

[4]
Differences in Distribution and Biological Effects of FO@PEG Nanoparticles in Normotensive and Hypertensive Rats-Focus on Vascular Function and Liver.

Biomedicines. 2021-12-7

[5]
Iron oxide nanoparticles aggravate hepatic steatosis and liver injury in nonalcoholic fatty liver disease through BMP-SMAD-mediated hepatic iron overload.

Nanotoxicology. 2021-8

[6]
Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats.

Biomedicines. 2021-4-2

[7]
Effect of iron oxide nanoparticles on vascular function and nitric oxide production in acute stress-exposed rats.

Physiol Res. 2020-12-22

[8]
The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection.

Int J Mol Sci. 2020-10-24

[9]
Sensitive SQUID Bio-Magnetometry for Determination and Differentiation of Biogenic Iron and Iron Oxide Nanoparticles in the Biological Samples.

Nanomaterials (Basel). 2020-10-9

[10]
Sympathetic Overactivation in Patients With Essential Hypertension and Hepatic Iron Overload.

Hypertension. 2020-11

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