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Accumulation of lipids and oxidatively damaged DNA in hepatocytes exposed to particles
- Source :
- Toxicology and Applied Pharmacology. 274:350-360
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Exposure to particles has been suggested to generate hepatosteatosis by oxidative stress mechanisms. We investigated lipid accumulation in cultured human hepatocytes (HepG2) and rat liver after exposure to four different carbon-based particles. HepG2 cells were exposed to particles for 3h and subsequently incubated for another 18h to manifest lipid accumulation. In an animal model of metabolic syndrome we investigated the association between intake of carbon black (CB, 14nm) particles and hepatic lipid accumulation, inflammation and gene expression of Srebp-1, Fasn and Scd-1 involved in lipid synthesis. There was a concentration-dependent increase in intracellular lipid content after exposure to CB in HepG2 cells, which was only observed after co-exposure to oleic/palmitic acid. Similar results were observed in HepG2 cells after exposure to diesel exhaust particles, fullerenes C60 or pristine single-walled carbon nanotubes. All four types of particles also generated oxidatively damaged DNA, assessed as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after 3h exposure. The animal model of metabolic syndrome showed increased lipid load in the liver after one oral exposure to 6.4mg/kg of CB in lean Zucker rats. This was not associated with increased iNOS staining in the liver, indicating that the oral CB exposure was associated with hepatic steatosis rather than steatohepatitis. The lipid accumulation did not seem to be related to increased lipogenesis because there were unaltered gene expression levels in both the HepG2 cells and rat livers. Collectively, exposure to particles is associated with oxidative stress and steatosis in hepatocytes.
- Subjects :
- DNA damage
Palmitic Acid
Nitric Oxide Synthase Type II
Toxicology
medicine.disease_cause
Soot
medicine
Animals
Humans
Vehicle Emissions
Inflammation
Pharmacology
chemistry.chemical_classification
Reactive oxygen species
Lipogenesis
Lipid metabolism
Hep G2 Cells
Formamidopyrimidine DNA glycosylase
medicine.disease
Molecular biology
Rats
Rats, Zucker
Fatty Acid Synthase, Type I
Fatty Liver
Comet assay
Oxidative Stress
DNA-Formamidopyrimidine Glycosylase
Liver
Biochemistry
chemistry
Hepatocytes
Fullerenes
Steatosis
Steatohepatitis
Reactive Oxygen Species
Sterol Regulatory Element Binding Protein 1
Stearoyl-CoA Desaturase
Oxidative stress
DNA Damage
Oleic Acid
Subjects
Details
- ISSN :
- 0041008X
- Volume :
- 274
- Database :
- OpenAIRE
- Journal :
- Toxicology and Applied Pharmacology
- Accession number :
- edsair.doi.dedup.....30476346423423abca6c80edb934877b