Herein, the hepatotoxicity in rats exposed BMS-907351 concentration to SWCNTs by intratracheal instillation was explored using a 1H NMR-based metabonomic approach to examine blood
plasma and liver tissue extracts obtained from rats treated with different SWCNTs concentrations. Concurrently, the toxic threshold and identification of potentially useful toxicity biomarkers of SWCNTs-induced hepatotoxicity were also studied by conventional clinical chemistry and histopathological examinations. Methods Single-walled carbon nanotubes and suspension preparation Non-functionalized SWCNTs, produced by CoMoCAT® (Sigma-Aldrich, St. Louis, MO, USA) catalytic CVD process, were purchased from Sigma-Aldrich, Inc. (St. Louis, MO, USA). Their diameter of 0.8 to 1.2 nm and a length of several microns were determined by transmission electron microscopy (TEM, JEM-2010FEF, JEOL, Ltd., Tokyo, Japan) selleck kinase inhibitor (Figure 1A). Raman spectroscopy had been used to assess purity (Raman spectrometer, RM200, SB431542 Renishaw, Gloucestershire, UK) (Figure 1B). The carbon content and the proportion of carbon as SWNT were above 90% and 70%, respectively. Figure 1 The non-functionalized SWCNTs. (A) TEM of SWCNTs. (B) Raman spectra of SWCNTs. SWCNTs samples at 150, 300, and 450 mg were dispersed in 20-mL
volumes of 0.9% sodium chloride solution, followed by ultrasonication at <50°C for 5 h. The resulting SWCNTs concentrations were 7.5, 15, and 22.5 mg/mL, respectively. Ethics statement All experiments involving the care and use of animals were performed in accordance with the guidelines and regulations concerning the ethics of science research in the Institute of Health and Environmental Medicine and approved by the Ethics Review Board of the Institute of Health and Environmental Medicine Cediranib (AZD2171) (approval number JKYSS-2009-018). Animals
and treatment Thirty healthy male Wistar rats (8 weeks of age, weight 180 to 220 g) were obtained from the Academy of Military Medical Sciences (Beijing, China). All procedures concerning animal usage were reviewed and approved by the Institutional Animal Care and Use Committee of the Academia. All rats were housed individually in metabolic cages and, throughout the study period, allowed food and tap water ad libitum, with light/dark cycles altering every 12 h, environment at 18°C to 22°C, and humidity from 40% to 60%. After 1 week of acclimatization, weight-matched rats were divided randomly into four groups (n = 6 per group) comprising a sodium chloride group (control) and low-, medium-, and high-concentration groups (7.5, 15, and 22.5 mg/kg body weight and named SWCNTs-L, M, and H, respectively). The rats were exposed to SWCNTs by intratracheal instillation of the corresponding SWCNTs suspensions once a day for 15 consecutive days, with the control group treated concurrently with 0.9% sodium chloride solution.