TY - JOUR

T1 - Hepatic Hazard Assessment of Silver Nanoparticle Exposure in Healthy and Chronically Alcohol Fed Mice

AU - Kermanizadeh, Ali

AU - Jacobsen, Nicklas R

AU - Roursgaard, Martin

AU - Loft, Steffen

AU - Møller, Peter

N1 - © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Silver (Ag) nanoparticles (NPs) are currently among one of the most widely used nanomaterials. This in turn, implies an increased risk of human and environmental exposure. Alcohol abuse is a global issue with millions of people in the general population affected by the associated adverse effects. The excessive consumption of alcohol is a prominent cause of chronic liver disease which manifest in multiple disorders. In this study, the adverse health effects of Ag NP exposure were investigated in models of alcoholic hepatic disease in vitro and in vivo. The data showed that Ag NP induced hepatic health effects were aggravated in the alcohol pretreated mice in comparison to controls with regards to an organ specific inflammatory response, changes in blood biochemistry, acute phase response and hepatic pathology. In addition, alcoholic disease influenced the organ's ability for recovery post-NP challenge. Additionally, it is demonstrated that the in vivo data correlated well with in vitro findings where ethanol pretreatment of hepatocytes resulted in significantly increased inflammatory response post-Ag NP exposure. To the best of our knowledge this is the first study of its kind to investigate nano-sized material-induced hepatic pathology in models representative of susceptible individuals (those with pre-existing alcohol liver disease) within the population. This is an area of research in the field of nanotoxicology, and in particular with regard to NP risk assessment that is almost entirely overlooked.

AB - Silver (Ag) nanoparticles (NPs) are currently among one of the most widely used nanomaterials. This in turn, implies an increased risk of human and environmental exposure. Alcohol abuse is a global issue with millions of people in the general population affected by the associated adverse effects. The excessive consumption of alcohol is a prominent cause of chronic liver disease which manifest in multiple disorders. In this study, the adverse health effects of Ag NP exposure were investigated in models of alcoholic hepatic disease in vitro and in vivo. The data showed that Ag NP induced hepatic health effects were aggravated in the alcohol pretreated mice in comparison to controls with regards to an organ specific inflammatory response, changes in blood biochemistry, acute phase response and hepatic pathology. In addition, alcoholic disease influenced the organ's ability for recovery post-NP challenge. Additionally, it is demonstrated that the in vivo data correlated well with in vitro findings where ethanol pretreatment of hepatocytes resulted in significantly increased inflammatory response post-Ag NP exposure. To the best of our knowledge this is the first study of its kind to investigate nano-sized material-induced hepatic pathology in models representative of susceptible individuals (those with pre-existing alcohol liver disease) within the population. This is an area of research in the field of nanotoxicology, and in particular with regard to NP risk assessment that is almost entirely overlooked.

KW - Acute-Phase Reaction

KW - Animals

KW - Antioxidants/metabolism

KW - Biomarkers/blood

KW - Chemical and Drug Induced Liver Injury

KW - Ethanol/administration & dosage

KW - Female

KW - Glutathione/metabolism

KW - Hep G2 Cells

KW - Humans

KW - Inflammation/chemically induced

KW - Interleukin-8/biosynthesis

KW - Liver/drug effects

KW - Liver Diseases, Alcoholic/pathology

KW - Metal Nanoparticles/chemistry

KW - Mice

KW - Silver/chemistry

U2 - 10.1093/toxsci/kfx080

DO - 10.1093/toxsci/kfx080

M3 - Article

C2 - 28453772

VL - 158

SP - 176

EP - 187

JO - Toxicological sciences

JF - Toxicological sciences

SN - 1096-0929

IS - 1

ER -