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

Abstract

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 (CeO 2 NPs) have emerged as a new antioxidant agent with hepatoprotective properties in experimental liver disease. The aim of the current investigation was to elucidate whether CeO 2 NPs 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 CeO 2 NP or vehicle during the weeks three and four of the diet. The effect of CeO 2 NPs 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 CeO 2 NPs 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 CeO 2 NPs could be of beneficial value in NAFLD.

Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

“…I,J) Reproduced with permission. [ 37a ] Copyright 2016, Elsevier Ltd. K,L) is part of our publication in Carvajal et al [ 110 ] Reproduced under the terms of the Creative Commons Attribution (CC BY) license, Copyright 2019, The Authors, published by Scientific Reports. For the NAFLD case, Wistar rats were subjected to methionine and choline deficient diet (MCDD) for 6 weeks and intravenously treated with CeO 2 NPs (0.1 mg kg −1 ) the weeks three and four of the diet.…”

“…CeO 2 NPs treatment (4 nm, albumin coated, 0.1 mg kg −1 ) of Wistar rats fed with a methionine and choline deficient diet for 6 weeks resulted in reduced liver inflammation and steatosis, suggesting the therapeutic value of these NPs in NAFLD. [ 110 ] In addition, the same type of CeO 2 NPs administered to Wistar rats with liver hepatocellular carcinoma (induced by a weekly i.p. injection of DEN for 16 weeks) improved overall survival, similar to the multikinase inhibitor sorafenib, which was associated with lower hepatic cell proliferation rate, less macrophage infiltration, specific changes in protein phosphorylation and several lipid components, and reduced levels of the tumor marker α‐fetoprotein.…”

Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes

“…Recently, we have demonstrated that CeO 2 NPs reduce steatosis, portal hypertension and display anti-inflammatory properties in rats with experimental liver fibrosis [12]. Also, we observed an antilipogenic and anti-inflammatory effect in the liver of rats subjected to a methionine and choline deficient diet for six weeks [13]. A major difference between antioxidants such as SOD or vitamin C and CeO 2 NPs is that the former two are rapidly oxidized or degraded (metabolized) whereas CeO 2 NPs act as self-renewal catalysts.…”

All Roads Lead to the Liver: Metal Nanoparticles and Their Implications for Liver Health

“…[104] Cerium oxide NPs (4-20 nm) were found to reduce NAFLD markers like steatosis, inflammation, and portal hypertension in rats with fibrotic livers, [45] with a follow-up paper reporting that lipid droplet size and content, fatty acid (FA) concentrations, and the expression of NAFLD-signaling pathways were reduced in cerium oxide NP-treated rats. [105] Another group reported a reduction in total lipid content and inflammation signals in cerium oxide NP-treated (1-5 nm) obese rats. [106] Furthermore, rats injected with cerium oxide (cubic, 5-80 nm) showed reduced weight gain, and reduced insulin, glucose, triglyceride, and leptin levels, demonstrating that cerium oxide NP were able to modulate metabolic profile in rats.…”

“…Second, studies revealed that not all exposure results in toxicity. Some NPS exhibit antioxidant, [167] antimicrobial, [116] and other pharmacological potentials toward liver pathology such as the amelioration of fatty liver, [105,106] antifibrotic, [42] as well as anticancer properties. [124,168] This implies that prudence must be exercised in the evaluation of toxicity reports, so that we do not categorically dismiss all NPs on the basis of a partial spectrum of toxicity data.…”