Intravenous Administration of Multiwalled Carbon Nanotubes Aggravates High-Fat Diet-Induced Nonalcoholic Steatohepatitis in Sprague Dawley Rats.
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.
Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Yu-Ying
YY
Xu
Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Juan
J
Ge
Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Mo-Han
MH
Zhang
Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Wen-Jie
WJ
Sun
Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Jun
J
Zhang
Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Pei-Lin
PL
Yu
Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China.
Yi-Fan
YF
Zheng
Department of Toxicology, School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, China gastate@zju.edu.cn zhuxq@zju.edu.cn.|Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, National Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
Jun
J
Yang
Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China gastate@zju.edu.cn zhuxq@zju.edu.cn.
Xin-Qiang
XQ
Zhu
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D059305:Diet, High-Fat; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000633:toxicity*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
D005230:Fatty Acids, Nonesterified; D037742:Nanotubes, Carbon; D014280:Triglycerides; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D005978:Glutathione
multiwalled carbon nanotubes; nonalcoholic fatty liver disease; oxidative stress; peroxiredoxin 6; steatohepatitis