The hepatotoxicity of multi-walled carbon nanotubes in mice.
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.
Ji
Zongfei
Z
Department of Gastroenterology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
Zhang
Danying
D
Li
Ling
L
Shen
Xizhong
X
Deng
Xiaoyong
X
Dong
Ling
L
Wu
Minhong
M
Liu
Yuanfang
Y
D000148:Acids, Noncarboxylic / Q000737:chemistry; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D001663:Bilirubin / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000148:Acids, Noncarboxylic; D037742:Nanotubes, Carbon; D011136:Polysorbates; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D001663:Bilirubin