Intravenous Administration of Multiwalled Carbon Nanotubes Aggravates High-Fat Diet-Induced Nonalcoholic Steatohepatitis in Sprague Dawley Rats

Int J Toxicol. 2016 Nov;35(6):634-643. doi: 10.1177/1091581816653363. Epub 2016 Jun 15.

Abstract

Multiwalled carbon nanotubes (MWCNTs) have been explored in pharmaceutical applications such as tumor targeting and delivery of drugs, in which MWCNTs are given through intravenous injection. However, the biosafety of MWCNTs is of concern for such application. Therefore, in the current study, we used a fatty liver model to investigate the possible toxicity of MWCNTs to the liver, as MWCNTs were retained mainly in the liver of mice after intravenous injection. Male Sprague Dawley rats were used to generate the fatty liver model, and the effects of intravenous administration of MWCNTs on fatty liver were studied. Hematoxylin and eosin staining for hepatocellular anatomy and Masson trichrome staining for hepatic fibrosis were conducted. Histologically, MWCNTs aggravated steatohepatitis with higher nonalcoholic fatty liver disease scores. Analysis of liver injury markers indicated that MWCNTs administration resulted in chronic hepatitis, along with increased liver fat and altered liver oxidation, including the increase of P6 protein and the depletion of glutathione. In conclusion, our results suggest that MWCNTs can aggravate nonalcoholic steatohepatitis in Sprague Dawley rats, and oxidative injury may be involved in this process.

Keywords: multiwalled carbon nanotubes; nonalcoholic fatty liver disease; oxidative stress; peroxiredoxin 6; steatohepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartate Aminotransferases / blood
  • Diet, High-Fat
  • Fatty Acids, Nonesterified / metabolism
  • Glutathione / metabolism
  • Glutathione Peroxidase / blood
  • Injections, Intravenous
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Nanotubes, Carbon / toxicity*
  • Non-alcoholic Fatty Liver Disease* / blood
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Triglycerides / metabolism
  • gamma-Glutamyltransferase / blood

Substances

  • Fatty Acids, Nonesterified
  • Nanotubes, Carbon
  • Triglycerides
  • Malondialdehyde
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Glutathione