AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD

The recent development of silver nanoparticles (AgNPs) has sparked increased interest in biomedical and pharmaceutical applications, leading to the possibility of human exposure. The liver is the primary target organ in the metabolism and transport of nanoparticles. Non-alcoholic fatty liver disease...

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Main Authors: Ling Wen, Minyan Li, Xiaojun Lin, Yan Li, Huidong Song, Hanqing Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.912178/full
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author Ling Wen
Minyan Li
Xiaojun Lin
Yan Li
Huidong Song
Hanqing Chen
author_facet Ling Wen
Minyan Li
Xiaojun Lin
Yan Li
Huidong Song
Hanqing Chen
author_sort Ling Wen
collection DOAJ
description The recent development of silver nanoparticles (AgNPs) has sparked increased interest in biomedical and pharmaceutical applications, leading to the possibility of human exposure. The liver is the primary target organ in the metabolism and transport of nanoparticles. Non-alcoholic fatty liver disease (NAFLD) is the most common and leading cause of hepatic metabolic syndrome with approximately 15% of patients will develop into non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Thus, the potential hepatotoxicity of AgNPs on NAFLD development and progression should be of great concern. Herein, we explored the potential hepatic effect of a single intravenously injected dose of 0.5, 2.5, and 12.5 mg/kg BW on the liver function of high-fat-diet (HFD)-fed mice for 7 days. AgNP treatment increased serum levels of alanine aminotransferase, aspartate transaminase, triglycerides and cholesterols, the number of lipid droplets, and the contents of triglycerides and cholesterols in NAFLD mice livers compared to HFD-fed mice. The mechanism of AgNP-induced worsen hepatotoxicity in mice is associated with hyperactivation of SREBP-1c-mediated de novo lipogenesis and liver inflammation. Additionally, HFD-fed mice treated with AgNPs had significantly higher oxidative damage and lower global DNA methylation and DNA hydroxymethylation than NAFLD mice. This study suggests that AgNP treatment exacerbated HFD-induced hepatic steatosis, liver inflammation, oxidative stress, and epigenetic changes in mice, which is relevant to the risk of AgNP exposure on NAFLD development and progression.
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spelling doaj.art-803cd4342ee54d2db592f1b520f12a7a2022-12-22T02:35:11ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-05-011010.3389/fbioe.2022.912178912178AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFDLing Wen0Minyan Li1Xiaojun Lin2Yan Li3Huidong Song4Hanqing Chen5Guangzhou Twelfth People’s Hospital, Guangzhou, ChinaGuangzhou Twelfth People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Twelfth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Twelfth People’s Hospital, Guangzhou, ChinaGuangzhou Twelfth People’s Hospital, Guangzhou, ChinaDepartment of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, ChinaThe recent development of silver nanoparticles (AgNPs) has sparked increased interest in biomedical and pharmaceutical applications, leading to the possibility of human exposure. The liver is the primary target organ in the metabolism and transport of nanoparticles. Non-alcoholic fatty liver disease (NAFLD) is the most common and leading cause of hepatic metabolic syndrome with approximately 15% of patients will develop into non-alcoholic steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Thus, the potential hepatotoxicity of AgNPs on NAFLD development and progression should be of great concern. Herein, we explored the potential hepatic effect of a single intravenously injected dose of 0.5, 2.5, and 12.5 mg/kg BW on the liver function of high-fat-diet (HFD)-fed mice for 7 days. AgNP treatment increased serum levels of alanine aminotransferase, aspartate transaminase, triglycerides and cholesterols, the number of lipid droplets, and the contents of triglycerides and cholesterols in NAFLD mice livers compared to HFD-fed mice. The mechanism of AgNP-induced worsen hepatotoxicity in mice is associated with hyperactivation of SREBP-1c-mediated de novo lipogenesis and liver inflammation. Additionally, HFD-fed mice treated with AgNPs had significantly higher oxidative damage and lower global DNA methylation and DNA hydroxymethylation than NAFLD mice. This study suggests that AgNP treatment exacerbated HFD-induced hepatic steatosis, liver inflammation, oxidative stress, and epigenetic changes in mice, which is relevant to the risk of AgNP exposure on NAFLD development and progression.https://www.frontiersin.org/articles/10.3389/fbioe.2022.912178/fullsilver nanoparticlesnon-alcoholic fatty liver diseasehepatic steatosisglobal DNA methylationliver inflammationhepatotoxicity
spellingShingle Ling Wen
Minyan Li
Xiaojun Lin
Yan Li
Huidong Song
Hanqing Chen
AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD
Frontiers in Bioengineering and Biotechnology
silver nanoparticles
non-alcoholic fatty liver disease
hepatic steatosis
global DNA methylation
liver inflammation
hepatotoxicity
title AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD
title_full AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD
title_fullStr AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD
title_full_unstemmed AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD
title_short AgNPs Aggravated Hepatic Steatosis, Inflammation, Oxidative Stress, and Epigenetic Changes in Mice With NAFLD Induced by HFD
title_sort agnps aggravated hepatic steatosis inflammation oxidative stress and epigenetic changes in mice with nafld induced by hfd
topic silver nanoparticles
non-alcoholic fatty liver disease
hepatic steatosis
global DNA methylation
liver inflammation
hepatotoxicity
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.912178/full
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