The hepatotoxicity of multi-walled carbon nanotubes in mice

Abstract

The hepatotoxicity of two types of multi-walled carbon nanotubes (MWCNTs), acid-oxidized MWCNTs (O-MWCNTs) and Tween-80-dispersed MWCNTs (T-MWCNTs), were investigated with Kunming mice exposed to 10 and 60 mg kg(-1) by intravenous injection for 15 and 60 d. Compared with the PBS group, the body-weight gain of the mice decreased and the level of total bilirubin and aspartate aminotransferase increased in the MWCNT-exposed group with a significant dose-effect relationship, while tumor necrosis factor alpha level did not show significant statistical change within 60 d. Spotty necrosis, inflammatory cell infiltration in portal region, hepatocyte mitochondria swelling and lysis were observed with a significant dose-effect relationship in the MWCNT groups. Liver damage of the T-MWCNT group was more severe than that of the O-MWCNT group according to the Roenigk classification system. Furthermore, T-MWCNTs induce slight liver oxidative damage in mice at 15 d, which was recovered at 60 d. Part of the gene expressions of mouse liver in the MWCNT groups changed compared to the PBS group, including GPCRs (G protein-coupled receptors), cholesterol biosynthesis, metabolism by cytochrome P450, natural-killer-cell-mediated cytotoxicity, TNF- alpha, NF-kappaB signaling pathway, etc. In the P450 pathway, the gene expressions of Gsta2 (down-regulated), Cyp2B19 (up-regulated) and Cyp2C50 (down-regulated) had significant changes in the MWCNT groups. These results show that a high dose of T-MWCNTs can induce hepatic toxicity in mice while O-MWCNTs seem to have less toxicity.

In vitro and in vivo toxicity assessment of nanoparticles

“…The study recognized the SW-CNTs as a respiratory toxicant, responsible for neurotoxicity and cell cycle defects. MW-CNTs are also known for increased micronuclei frequency and chromosomal aberrations, promotion of allergic response in mice, activation of cyclooxygenase enzymes through suppression of systemic immune function in spleen and altered gene expression in the liver [173][174][175][176][177]. Other effects of MW-CNTs include apoptosis, phenotypic defects, toxicity in bacteria and formation of abnormal spinal cords in zebrafish embryo [178][179][180].…”

<div>Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway</div>

“…23 Another study suggested that multi-walled carbon nanotubes (MWNTs) injected via the intravenous route could cause mitochondrial destruction, spotty necrosis, and infiltration of inflammatory cells in the mouse liver. 24 Furthermore, intravenous exposure to high doses of CNTs might cause reproductive toxicity and embryotoxicity. 25,26 These controversial results are suggested to be associated with varied physicochemical properties of CNTs and exposure doses and time that may influence their toxicity profile.…”

Carbon nanotubes: Properties, biomedical applications, advantages and risks in patients and occupationally-exposed workers

“…47 Moreover, Ji et al found that gene expressions for GPCRs (G protein-coupled receptors), cholesterol biosynthesis, the metabolism by cytochrome P450, the natural-killer-cellmediated cytotoxicity, TNF-alpha, and NF-kappaB signaling pathway changed in mouse liver exposed to MWCNT. 48 …”