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 (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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, ranging from steatosis to non-alcoholic steatohepatitis (NASH)
In the current study we explored the impact of CeO2NPs on steatosis by assessing the liver histology and fatty acid content, macrophage infiltration and the expression of genes involved in inflammation, reactive oxygen species (ROS) and lipid metabolism in the methionine and choline deficient diet (MCDD) experimental model of NAFLD in rats
HR-TEM at low magnification revealed loose CeO2NPs agglomerates, and the X-ray diffraction pattern of CeO2NPs showed pure nanoparticles with the typical peak broadening characteristic of nanosize particles
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, ranging from steatosis to non-alcoholic steatohepatitis (NASH). 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. 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. CeO2NPs are only active at pathogenic levels of ROS, being inert and innocuous in healthy cells[31] In this regard, previous investigations indicated that CeO2NPs are able to reduce steatosis[30], attenuate oxidative stress[32,33,34] and display anti-inflammatory properties[30,35,36] in different experimental models of liver disease. It does not resemble the metabolic profile and etiology of human NAFLD, it mimics several of the histopathological features of human NAFLD37,38
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