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氧化铈纳米颗粒:肝脏疾病治疗的新工具。

Cerium Oxide Nanoparticles: A New Therapeutic Tool in Liver Diseases.

作者信息

Casals Gregori, Perramón Meritxell, Casals Eudald, Portolés Irene, Fernández-Varo Guillermo, Morales-Ruiz Manuel, Puntes Victor, Jiménez Wladimiro

机构信息

Service of Biochemistry and Molecular Genetics, Hospital Clinic Universitari, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions, Biomèdiques August Pi i Sunyer (IDIBAPS), 08905 Barcelona, Spain.

Comission for the Biochemical Assessment of Hepatic Disease-SEQCML, 08036 Barcelona, Spain.

出版信息

Antioxidants (Basel). 2021 Apr 24;10(5):660. doi: 10.3390/antiox10050660.

Abstract

Oxidative stress induced by the overproduction of free radicals or reactive oxygen species (ROS) has been considered as a key pathogenic mechanism contributing to the initiation and progression of injury in liver diseases. Consequently, during the last few years antioxidant substances, such as superoxide dismutase (SOD), resveratrol, colchicine, eugenol, and vitamins E and C have received increasing interest as potential therapeutic agents in chronic liver diseases. These substances have demonstrated their efficacy in equilibrating hepatic ROS metabolism and thereby improving liver functionality. However, many of these agents have not successfully passed the scrutiny of clinical trials for the prevention and treatment of various diseases, mainly due to their unspecificity and consequent uncontrolled side effects, since a minimal level of ROS is needed for normal functioning. Recently, cerium oxide nanoparticles (CeONPs) have emerged as a new powerful antioxidant agent with therapeutic properties in experimental liver disease. CeONPs have been reported to act as a ROS and reactive nitrogen species (RNS) scavenger and to have multi-enzyme mimetic activity, including SOD activity (deprotionation of superoxide anion into oxygen and hydrogen peroxide), catalase activity (conversion of hydrogen peroxide into oxygen and water), and peroxidase activity (reducing hydrogen peroxide into hydroxyl radicals). Consequently, the beneficial effects of CeONPs treatment have been reported in many different medical fields other than hepatology, including neurology, ophthalmology, cardiology, and oncology. Unlike other antioxidants, CeONPs are only active at pathogenic levels of ROS, being inert and innocuous in healthy cells. In the current article, we review the potential of CeONPs in several experimental models of liver disease and their safety as a therapeutic agent in humans as well.

摘要

自由基或活性氧(ROS)过量产生所诱导的氧化应激被认为是导致肝脏疾病损伤起始和进展的关键致病机制。因此,在过去几年中,超氧化物歧化酶(SOD)、白藜芦醇、秋水仙碱、丁香酚以及维生素E和C等抗氧化物质作为慢性肝病的潜在治疗药物受到了越来越多的关注。这些物质已证明它们在平衡肝脏ROS代谢从而改善肝功能方面的功效。然而,这些药物中的许多未能成功通过预防和治疗各种疾病的临床试验审查,主要是因为它们缺乏特异性,从而导致副作用无法控制,因为正常功能需要最低水平的ROS。最近,氧化铈纳米颗粒(CeONPs)已成为一种新型强效抗氧化剂,在实验性肝病中具有治疗特性。据报道,CeONPs可作为ROS和活性氮物质(RNS)的清除剂,并具有多酶模拟活性,包括SOD活性(将超氧阴离子去质子化为氧气和过氧化氢)、过氧化氢酶活性(将过氧化氢转化为氧气和水)以及过氧化物酶活性(将过氧化氢还原为羟基自由基)。因此,除肝病学外,CeONPs治疗的有益效果在神经学、眼科、心脏病学和肿瘤学等许多不同医学领域也有报道。与其他抗氧化剂不同,CeONPs仅在ROS的致病水平下具有活性,在健康细胞中呈惰性且无害。在本文中,我们综述了CeONPs在几种肝病实验模型中的潜力以及它们作为人类治疗药物的安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d382/8146351/1841cc812431/antioxidants-10-00660-g001.jpg

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