Cerium oxide nanoparticles reduce steatosis, portal hypertension and display anti-inflammatory properties in rats with liver fibrosis

被引：170
作者：
Oro, Denise [1 ]
Yudina, Tetyana [2 ]
Fernandez-Varo, Guillermo [1 ,5 ]
Casals, Eudald [2 ]
Reichenbach, Vedrana [1 ]
Casals, Gregori [1 ]
Gonzalez de la Presa, Bernardino [1 ]
Sandalinas, Silvia [1 ]
Carvajal, Silvia [1 ]
Puntes, Victor [2 ,3 ,4 ]
Jimenez, Wladimiro [1 ,5 ]
机构：
[1] Hosp Clin Univ, IDIBAPS, CIBERehd, Biochem & Mol Genet Serv, Barcelona, Spain
[2] Inst Catala Nanociencia & Nanotecnol ICN2, Bellaterra, Spain
[3] Inst Catala Recerca & Estudis Avancats, Barcelona, Spain
[4] Vall dHebron Insitute Res VHIR, Barcelona, Spain
[5] Univ Barcelona, Dept Ciencies Fisiol 1, Barcelona, Spain
来源：
JOURNAL OF HEPATOLOGY | 2016年 / 64卷 / 03期
关键词：
Experimental fibrosis; Oxidative stress; Cerium oxide nanoparticles; Portal pressure; Hepatic inflammation; PROLIFERATOR-ACTIVATED RECEPTORS; OXIDATIVE STRESS; MECHANISMS; INFLAMMATION; RESOLUTION; NANOCERIA; TOXICITY; DISEASE; MODEL;
D O I：
10.1016/j.jhep.2015.10.020
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Background & Aims: Cerium oxide nanoparticles (CeO(2)NPs) have proven to behave as free radical scavengers and/or anti-inflammatory agents. The aim of the study was to determine whether CeO(2)NPs display hepatoprotective properties in experimental chronic liver disease. Methods: Systemic and hepatic effects of nanoparticles were assessed in CCl4-treated rats receiving CeO(2)NPs or vehicle twice weekly for two weeks and CCl4 treatment was continued for 8 additional weeks. Thereafter, mean arterial pressure and portal pressure (PP) were assessed and serum samples obtained to measure standard hepatic and renal function tests. Organ and subcellular distribution of NPs were assessed using mass spectrometry (ICP-MS) and transmission electron microscopy. Liver samples were obtained to evaluate steatosis, alpha-SMA expression, macrophage infiltration, apoptosis and mRNA expression of oxidative stress, inflammatory or vasoactive related genes. Results: Most CeO(2)NPs were located in the liver and it reduced hepatic steatosis, ameliorated systemic inflammatory biomarkers and improved PP without affecting mean arterial pressure. In addition, a marked reduction in mRNA expression of inflammatory cytokines (TNF alpha, IL1 beta, COX-2, iNOS), ET-1 and messengers related to oxidative (Epx, Ncf1, Ncf2) or endoplasmic reticulum (Atf3, Hspa5) stress signaling pathways was observed in the liver of rats receiving CeO(2)NPs. This was associated with reduced macrophage infiltration and reduced abundance of caspase-3, a-SMA and inflammatory cytokines. Conclusions: CeO(2)NPs administration to CCl4-treated rats protects against chronic liver injury by reducing liver steatosis and portal hypertension and markedly attenuating the intensity of the inflammatory response, thereby suggesting that CeO(2)NPs may be of therapeutic value in chronic liver disease. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：691 / 698
页数：8
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