Subchronic toxicity and cardiovascular responses in spontaneously hypertensive rats after exposure to multiwalled carbon nanotubes by intratracheal instillation

Chem Res Toxicol. 2015 Mar 16;28(3):440-50. doi: 10.1021/tx5004003. Epub 2015 Jan 22.

Abstract

The tremendous demand of the market for carbon nanotubes has led to their massive production that presents an increasing risk through occupational exposure. Lung deposition of carbon nanotubes is known to cause acute localized pulmonary adverse effects. However, systemic cardiovascular damages associated with acute pulmonary lesion have not been thoroughly addressed. Four kinds of multiwalled carbon nanotubes (MWCNTs) with different lengths and/or iron contents were used to explore the potential subchronic toxicological effects in spontaneously hypertensive (SH) rats and normotensive control Wistar-Kyoto (WKY) rats after intratracheal instillation. MWCNTs penetrated the lung blood-gas barrier and accumulated in the liver, kidneys, and spleen but not in the heart and aorta of SH rats. The pulmonary toxicity and cardiovascular effects were assessed at 7 and 30 days postexposure. Compared to the WKY rats, transient influences on blood pressure and up to 30 days persistent decrease in the heart rate of SH rats were found by electrocardiogram monitoring. The subchronic toxicity, especially the sustained inflammation of the pulmonary and cardiovascular system, was revealed at days 7 and 30 in both SH and WKY rat models. Histopathological results showed obvious morphological lesions in abdominal arteries of SH rats 30 days after exposure. Our results suggest that more attention should be paid to the long-term toxic effects of MWCNTs, and particularly, occupationally exposed workers with preexisting cardiovascular diseases should be monitored more thoroughly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Blood Pressure / drug effects
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • C-Reactive Protein / analysis
  • Electrocardiography
  • Fibrinogen / analysis
  • Heart Rate / drug effects
  • Hypertension / metabolism*
  • Hypertension / pathology
  • Intercellular Adhesion Molecule-1 / blood
  • Iron / chemistry
  • Iron / toxicity
  • Kidney / metabolism
  • L-Lactate Dehydrogenase
  • Leukocyte Count
  • Liver / metabolism
  • Lung / drug effects*
  • Lung / pathology
  • Lung / ultrastructure
  • Male
  • Nanotubes, Carbon / chemistry
  • Nanotubes, Carbon / toxicity*
  • Peptidyl-Dipeptidase A / blood
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Spleen / metabolism
  • Tumor Necrosis Factor-alpha
  • Uteroglobin
  • von Willebrand Factor / analysis

Substances

  • Nanotubes, Carbon
  • Tumor Necrosis Factor-alpha
  • von Willebrand Factor
  • Intercellular Adhesion Molecule-1
  • Fibrinogen
  • C-Reactive Protein
  • Uteroglobin
  • Iron
  • L-Lactate Dehydrogenase
  • Peptidyl-Dipeptidase A