Cerium oxide nanoparticles display antilipogenic effect in rats with non-alcoholic fatty liver disease

Abstract

Cerium oxide nanoparticles; Non-alcoholic fatty liver disease; Antioxidant agent

Nanopartículas de óxido de cerio; Enfermedad del hígado graso no alcohólico; Agente antioxidante

Nanopartícules d’òxid de ceri; Malalties hepàtiques no alcohòliques; Agent antioxidant

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, ranging from steatosis to non-alcoholic steatohepatitis (NASH). Recently, cerium oxide nanoparticles (CeO2NPs) have emerged as a new antioxidant agent with hepatoprotective properties in experimental liver disease. The aim of the current investigation was to elucidate whether CeO2NPs display beneficial effects in an experimental model of NAFLD.Therefore, fifteen Wistar rats were subjected to a methionine and choline deficient diet (MCDD) for 6 weeks and intravenously treated with CeO2NP or vehicle during the weeks three and four of the diet. The effect of CeO2NPs on serum biochemistry, hepatic steatosis, inflammation, fatty acid content and expression of reactive oxygen species (ROS) and lipid metabolism related genes was assessed. MCDD fed rats showed increased inflammation, enhanced hepatic lipid accumulation of both saturated and unsaturated fatty acids (FAs) and overexpression of genes related to fatty liver and ROS metabolism. Treatment with CeO2NPs was able to reduce the size and content of hepatocyte lipid droplets, the hepatic concentration of triglyceride- and cholesterol ester-derived FAs and the expression of several genes involved in cytokine, adipokine and chemokine signaling pathways. These findings suggest that CeO2NPs could be of beneficial value in NAFLD.

This research was supported by grants to W. Jiménez from Ministerio de Economia y Competitividad [grants SAF2015-64126R, 12-35979, BES-2013-063685, SAFRTI2018-094734-B-C21], to M. Morales-Ruiz [grant SAF2016-75358-R] and to G. Casals [grant P74844I/15/00777]; Cofinanced by FEDER, European Union, a way of making Europe, Agència de Gestió d’Ajuts Universitaris i de Recerca [grant SGR 2014/219]. The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Instituto de Salud Carlos III.