Subchronic Toxicity and Cardiovascular Responses in Spontaneously Hypertensive Rats after Exposure to Multiwalled Carbon Nanotubes by Intratracheal Instillation

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.

Effects of Multiwalled Carbon Nanotube Surface Modification and Purification on Bovine Serum Albumin Binding and Biological Responses

“…For example, we have previously reported that MWCNTs with a length of 10–100 μm impaired pulmonary function [42] and induced severe cardiac ischemic/reperfusion injury after pulmonary instillation [43]. Similar results on MWCNT toxicity have been reported [44–47]. However, it is being recognized that toxicity induced by carbon nanotubes is highly dependent on their length and functionalization.…”

Defect density in multiwalled carbon nanotubes influences ovalbumin adsorption and promotes macrophage activation and CD4^+ T-cell proliferation

“…For example, our earlier studies found that MWCNTs with a length of 10-100 μm impaired pulmonary function 22 and induced severe cardiac ischemic/ reperfusion injury after pulmonary instillation. 23 Similar results on MWCNT toxicity were also reported elsewhere, [24][25][26][27] such as subchronic toxicity, asbestos-like pathogenicity in mice, and airway fibrosis. In contrast, CNTs with a length shorter than 2 μm have been shown to exhibit minimal toxicity to various cell types, such as human promyelocytic leukemia (HL60) and human T-cells (Jurkat).…”

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

“…SW-CNTs (Li et al, 2007) and MW-CNTs (Xu et al, 2012) as well as nickel hydroxide-NPs (Kang et al, 2011) were able to accelerate the atherosclerosis progression in aortas of in vivo susceptible models. More recently, MW-CNTs were reported to induce a transient decrease in blood pressure, a long-term reduction in the heart rate as well as structural changes in large arteries in spontaneously hypertensive rats compared to healthy animals (Chen et al, 2015). These results are in line with epidemiological findings that have implicated particulate air pollution, and specifically its ultrafine size fraction, as an important contributor to morbidity and mortality from cardiovascular causes (Peters et al, 2011).…”