title: Susceptibility to gold nanoparticle-induced hepatotoxicity is enhanced in a mouse model of nonalcoholic steatohepatitis.
abstract: Although the safety of gold nanoparticle (AuNP) use is of growing concern, most toxicity studies of AuNPs had focused on their chemical characteristics, including their physical dimensions, surface chemistry, and shape. The present study examined the susceptibility of rodents with healthy or damaged livers to AuNP-induced hepatotoxicity. To induce a model of liver injury, mice were fed a methionine- and choline-deficient (MCD) diet for 4 weeks. Sizes and biodistribution of 15-nm PEGylated AuNPs were analyzed by transmission electron microscopy. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were estimated with an automatic chemical analyzer, and liver sections were subjected to pathological examination. Activities of antioxidant enzymes were determined by biochemical assay. Lateral tail vein injection of MCD diet-fed mice with 5 mg kg(-1) AuNPs significantly elevated the serum ALT and AST levels compared to MCD diet-fed mice injected with mPEG (methylpolyethylene glycol). Similarly, severe hepatic cell damage, acute inflammation, and increased apoptosis and reactive oxygen species (ROS) production were observed in the livers of AuNP-injected mice on the MCD diet; these liver injuries were attenuated in mice fed a normal chow diet. The results suggest that AuNPs display toxicity in a stressed liver environment by stimulating the inflammatory response and accelerating stress-induced apoptosis. These conclusions may point to the importance of considering health conditions, including liver damage, in medical applications of AuNPs.
authors.affiliation: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro 125, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Hwang
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Jung-Ran
authors.initials: JR
authors.lastname: Noh
authors.forename: Gil-Tae
authors.initials: GT
authors.lastname: Gang
authors.forename: Bong Hyun
authors.initials: BH
authors.lastname: Chung
authors.forename: Nam Woong
authors.initials: NW
authors.lastname: Song
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005234:Fatty Liver / Q000150:complications* / Q000473:pathology; D017612:Gold Compounds / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D017382:Reactive Oxygen Species / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017612:Gold Compounds; D017382:Reactive Oxygen Species; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase