The Influence Of Multi-walled Nanotubes On Mice Liver And Urine Metabolism

Objective:With the development of nanoscience,carbon nanotubes are widely used in medicine field,accordingly,more and more attentions are paid to their security.There are many studies and reports on nanotoxicity both in home and abroad,among which the biocompatibility of carbon nanotubes is an important factor that results in toxicity to organism,thus carbon nanotubes are needed to improve their biocompatibility by modification to reduce their toxicity,and these new types of carbon nanotubes are used as drug carriers and biosensors etc.Although some pilot reports found that some modified carbon nanotubes showed no toxicity to organism in vivo,the detailed toxicology data was still lack.Our test is to investigate carbon nanotubes toxicology effect through researches on the influences of multi-walled carbon nanotubes and modified multi-walled carbon nanotubes in mice by liver injures detection and urine metabolism analysis.Methods:Prepare for MWCNT-COOH and MWCNT-PEG and determine their characteristics. Select 70 mice and divide them into seven groups as following:phosphate buffered saline group,multiwalled carbon nanotubes group(contain two different dosages:10 millgram per kilogram and 60 millgram per kilogram),polyethylene glycolylated carbon nanotubes group(contain two different dosages:10 millgram per kilogram and 60 millgram per kilogram),carboxylated multiwalled carbon nanotubes group (contain two different doses:10 millgram per kilogram and 60 millgram per kilogram),10 mice in each group.Drugs were injected i.v.into the tail caudal vein with the rate of 1mL per minute.We collected 24 hour urine of mice's half of each group by metabolic cages at 14 days and 59 days respectively,and executed mice of different groups to collect serums and liver tissues for whole specimens as well as pathological sections observation and for serum TB,ALT,AST,Cr as well as SOD,GSH of liver tissues determination.We applied ECF to urine sample derivatization, analyzed urine metabolism by gas-chromatography-mass spectrometry and analyzed urine metabolisms with GC-MS technique.Results:1.Liver injures:â‘ Compared with PBS group,we found more nanotubes deposition in 60 days liver tissues than in 15days liver tissues of the rest groups,and more focus necrosises in HE stain of pathology tissue.Within the same breeding time(15days and 60days),we found more nanotubes depositions in liver tissues of different administrationed groups with a dosage of 60mg/kg than those with a dosage of 10mg/kg,HE stain of pathology tissue revealed that there were mild inflammation cell infiltration at portal vein area,spotty necrosis or small focal necrosis among a small quantity liver cells,especially in pristine group,while there were focal necrosis among a small quantity liver cells in PEG group,no obvious liver pathological changes were found in other groups.â‘¡At the breeding time of 15 days and 60 days, we found the value of AST was rised among administrationed groups compared with PBS group,which indicated liver injures.There were no significant differences of Cr among administrationed groups compared with PBS group.â‘¢At the breeding time of 15 days and 60 days,there were no significant differences of SOD and GSH among different groups with the same dosage and different dosages of the same group.2.Influence on urine metabolism:â‘ At the breeding time of 15 days and 60 days, there were no significant differences of urine metabolisms among control group,MWCNT group,MWCNT-COOH group and MWCNT-PEG group.â‘¡At the breeding time of 15 days and 60 days,there were no significant differences of urine metabolisms between high dosage group and low dosage group of all the three administrationed groups.â‘¢There were significant differences of urine metabolisms between pristine group at the breeding time of 60 days,so did PEG group,but we also found significant differences of urine metabolisms between the control group at the breeding time of 15 days and those at the breeding time of 60 days,which indicated that such differences maybe dose no mean to our toxicology research.Conclution:1.Pristine multiwalled carbon nanotubes result in mild liver injures,and these injures can be reduced by COOH and PEG modification.3.There were no significant differences of low molecular urine metabolisms among pristine and modificated multiwalled carbon nanotubes groups.