ABSTRACT
The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics.The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs.SD rats were randomly divided into seven groups,including control group,three doses (40,200,1 000 mg/kg) of relegar and realgar NPs groups,respectly.After 28 days of continuous intragastric administration,all rats were sacrificed and their serum and kidney samples were collected.The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination,which revealed a dosedependent nephrotoxicity induced by realgar NPs.The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study.A series of 32 metabolites were found to be altered significandy in the kindey of realgar NPs treated rats,and might serve as potential nephrotoxicity biomarkers.The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.
ABSTRACT
Objective To establish a RP-HPLC fingerprinting analysis method for quality evaluation and control of the four variants of Chrysanthemi Morifoli Flos. Methods RP-HPLC was used to establish the fingerprinting method.Results Despite of the similarity in terms of holistic HPLC chromatograms, the four variants of Chrysanthemi Morifoli Flos exhibit characteristic fingerprints and can be readily recognized by similarity clusters. Conclusion A simple and reliable HPLC fingerprinting method has been developed and validated to authenticate the four variants of Chrysanthemi Morifoli Flos, providing a scientific basis for quality control of Chrysanthemi Morifoli Flos.
ABSTRACT
Objective To study the anti-tumor effect and liver toxicity of Oxaliplatin (L-OHP)from different outflow tracts, we implemented isolated perfusion on rabbit VX2 tumor model with L-OHP.Methods In this study, 60 rabbits in which VX2 liver cancer were established were randomly divided into three groups ( A = B = C = 20). Group A and B were taken isolated hepatic perfusion with 5 mg/kg L-OHP,while group C was normal control, which was taken isolated hepatic perfusion without L-OHP. Perfusion fluid flowed through the hepatic veins in group A, while in group B and C perfusion fluid flowed through the portal vein. Blood biochemistry、liver histopathology 、vascular endothelial growth factor (VEGF) expression and hepatocyte apoptosis index (AI) in the postoperative 6th and 12th hour were examined. L-OHP concentration was measured during the perfusion with RP-HPLC in group A and B. Results Serum ALT、AST rose significantly in all three groups in the 6th and 12th hour postoperatively, and that in group A was higher than either group B or C. Differences in serum ALT、AST level between group A and B, B and C, A and C were all statistically significant (tALT = 2. 328、tALT =7. 116、tALT =3. 124,P ＜ 0.05;tAST =2.547、tAST =4. 710、tAST = 2. 238, P ＜ 0. 05 ). The differences of L-OHP concentration in the liver and systemic circulation between group A and B was statistically significant(t =3.091, P ＜0. 05;t =2. 778,P ＜0. 05),however the difference between group A and B of L-OHP concentration in the tumor tissue and outflow tract was not statistically significant( t = 1. 461, P ＞ 0. 05; t = 0. 223, P ＞ 0. 05 ). Hepatic pathology in group A was more serious than that in group B in the 12th hour postoperatively. The levels of VEGF expression in liver tumor tissue in postoperative 12th hour, in group A and B were significantly lower comparing with group C (tAC =2.728, P ＜ 0.05;tBC =3.397,P ＜0.01). Between group A and B, the difference was not statistically significant ( t = 0. 591, P ＞ 0. 05 ). Differences in hepatocyte apoptosis index ( AI ) in the postoperative 12th hour between group A and C, A and B, B and C were all statistically significant( tAB=3. 689, P ＜ 0. 01 ;tAC = 5. 067, P ＜ 0. 01 ;tBC = 2. 607, P ＜ 0. 05 ), and with that in group A being higher than either in group B or C. Conclusions L-OHP had a significant anti-tumor effect in isolated hepatic perfusion; Chemotherapy infusion fluid flowing through the portal vein retrogradely was a more complete and safer way of regional chemotherapy than antegrade flowing through the hepatic vein.