scholarly journals The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yanyan Xu ◽  
Yiwei Zhao ◽  
Jiabin Xie ◽  
Xue Sheng ◽  
Yubo Li ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Safety Evaluation ◽  
Rat Plasma ◽  
Leguminous Plant ◽  
Control Group ◽  
Kidney Toxicity ◽  
Flight Mass Spectrometry ◽  
Liver And Kidney ◽  
Tof Ms

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.

scholarly journals A Study of the Identification, Fragmentation Mode and Metabolic Pathways of Imatinib in Rats Using UHPLC-Q-TOF-MS/MS

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Sijiang Liu ◽  
Zhaojin Yu
Keyword(s):  
Metabolic Pathways ◽  
High Performance ◽  
Kinase Inhibitor ◽  
Solid Phase ◽  
Rat Plasma ◽  
Amide Bond ◽  
Catalytic Dehydrogenation ◽  
Fragmentation Pattern ◽  
Flight Mass Spectrometry ◽  
Tof Ms

In this study, The metabolites, metabolic pathways, and metabolic fragmentation mode of a tyrosine kinase inhibitor- (TKI-) imatinib in rats were investigated. The samples for analysis were pretreated via solid-phase extraction, and the metabolism of imatinib in rats was studied using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Eighteen imatinib metabolites were identified in rat plasma, 21 in bile, 18 in urine, and 12 in feces. Twenty-seven of the above compounds were confirmed as metabolites of imatinib and 9 of them were newly discovered for the first time. Oxidation, hydroxylation, dealkylation, and catalytic dehydrogenation are the main metabolic pathways in phase I. For phase II, the main metabolic pathways were N-acetylation, methylation, cysteine, and glucuronidation binding. The fragment ions of imatinib and its metabolites were confirmed to be produced by the cleavage of the C-N bond at the amide bond. The newly discovered metabolite of imatinib was identified by UHPLC-Q-TOF-MS/MS. The metabolic pathway of imatinib and its fragmentation pattern were summarized. These results could be helpful to study the safety of imatinib for clinical use.

scholarly journals An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2894 ◽  
Author(s):  
Song-Tao Dong ◽  
Ying Li ◽  
Hao-Tian Yang ◽  
Yin Wu ◽  
Ya-Jing Li ◽  
...  
Keyword(s):  
Matrix Effects ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Analysis Method ◽  
T790m Mutation ◽  
Flight Mass Spectrometry ◽  
Relative Standard ◽  
New Generation ◽  
Tof Ms

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.

scholarly journals Analysis of Serum Metabolomics in Rats with Osteoarthritis by Mass Spectrometry

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7181
Author(s):  
Jingtong Zhao ◽  
Meng Liu ◽  
Tongfei Shi ◽  
Mohan Gao ◽  
Yuqian Lv ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Principal Component ◽  
Male Rats ◽  
Control Group ◽  
Liquid Chromatography Mass Spectrometry ◽  
Disease Mechanisms ◽  
Periarticular Tissue ◽  
Serum Metabolomics

Osteoarthritis is a common multifactorial chronic disease that occurs in articular cartilage, subchondral bone, and periarticular tissue. The pathogenesis of OA is still unclear. To investigate the differences in serum metabolites between OA and the control group, liquid chromatography/mass spectrometry (LC/MS)-based metabolomics was used. To reveal the pathogenesis of OA, 12 SD male rats were randomly divided into control and OA groups using collagenase to induce OA for modeling, and serum was collected 7 days after modeling for testing. The OA group was distinguished from the control group by principal component analysis and orthogonal partial least squares-discriminant analysis, and six biomarkers were finally identified. These biomarkers were metabolized through tryptophan metabolism, glutamate metabolism, nitrogen metabolism, spermidine metabolism, and fatty acid metabolism pathways. The study identified metabolites that may be altered in OA, suggesting a role in OA through relevant metabolic pathways. Metabolomics, as an important tool for studying disease mechanisms, provides useful information for studying the metabolic mechanisms of OA.

scholarly journals Biochemical and Molecular Studies on the Role of Rosemary (Rosmarinus officinalis) Extract in Reducing Liver and Kidney Toxicity Due to Etoposide in Male Rats

2019 ◽  
pp. 1-11
Author(s):  
Majd Almakhatreh ◽  
Ezar Hafez ◽  
Ehab Tousson ◽  
Ahmed Masoud
Keyword(s):  
Dna Damage ◽  
Calcium Ions ◽  
Chloride Ions ◽  
Male Rats ◽  
Control Group ◽  
Potassium Ions ◽  
Sodium Ions ◽  
Total Proteins ◽  
Kidney Toxicity ◽  
Liver And Kidney

Aims: Etoposide (Vepesid) is chemotherapeutic drugs that inhibit topoisomerase II activity and long been used for treatment of human malignancies, where it is a semi-synthetic compound derived from the plant Podophyllum peltatum. The current study was designed to investigate the possible protective effect of rosemary extract against Etoposide -induced changes in liver and kidney functions, and DNA damage in rats. Materials and Methods: A total of 50 male Wistar albino rats were divided randomly into four groups (1st group was control; 2nd group was treated with rosemary, 3rd group was received etoposide, and 4th & 5th groups was co- and post treated groups respectively). Results: The administration of Etoposide revealed a significant increase in serum ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage. In contrast; a significant decrease in albumen, total proteins, sodium ions, and calcium ions were when compared with control group. This increased in ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage was reduced after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide  (G5) for four weeks with lowest damage in G4. Also, this decreased in albumen, total proteins, sodium ions, and calcium ions was increased after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide (G5) for four weeks with lowest damage in G4. Conclusion: It could be concluded that rosemary has a promising role and it worth to be considered as a natural substance for protective the liver and kidney toxicity induced by etoposide (Vepesid) chemotherapy.

Xuebijing Injection Affects the Dynamic Change of Metabolism in CLP-Induced Septic Rats

2021 ◽  
Author(s):  
Yanjuan Liu ◽  
Qi Zeng ◽  
Wen Xiao ◽  
Fang Chen ◽  
Lianhong Zou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Dynamic Change ◽  
Sepsis Group ◽  
Control Group ◽  
Multivariate Statistical ◽  
Xuebijing Injection ◽  
Kegg Pathway Analysis

Abstract Xuebijing injection has been widely applied to treat sepsis. However, its roles in the dynamic change of metabolism in sepsis are still unknown. In our study, Gas chromatography-mass spectrometer (GC-MS) combined with multivariate statistical techniques was used to detect the metabolic change in septic rats with or without XBJ injection treatment. The KEGG pathway analysis was used to further analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change, variable important in projection, and P value, we found 11, 33 and 26 differential metabolites in the sepsis group at 2, 6 and 12 hours post CLP, compared with the control group. Besides, we also found 32, 23 and 28 differential metabolites in the XBJ group at 2, 6 and 12 hours post CLP. The related pathways of differential metabolites were glycometabolism at 2h, glycometabolism and amino acid metabolism at 6h and amino acid metabolism at 12h post CLP in the sepsis group compared with the control group. Besides, glycometabolism, amino acid metabolism and lipid metabolism changed markedly after XBJ injection for 2 hours; while only amino acid metabolism changed significantly with the treatment of XBJ injection for 6 and 12 hours, compared with the sepsis group. Further analysis showed 3, 6 and 6 differential metabolites were overlapped in the sepsis group and XBJ group at 2, 6 and 12 hours post CLP. These identified differential metabolites were majorly involved in arginine and proline metabolism, suggesting that XBJ injection is capable of improving metabolic disorders in CLP-induced septic rat to a certain extent.

scholarly journals A Serum Metabolic Profiling Analysis During the Formation of Fatty Liver in Landes Geese via GC-TOF/MS

2020 ◽  
Vol 11 ◽  
Author(s):  
Yujie Gong ◽  
Wentao Lyu ◽  
Xingfen Shi ◽  
Xiaoting Zou ◽  
Lizhi Lu ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Metabolic Pathways ◽  
Liver Steatosis ◽  
Liver Weight ◽  
The Body ◽  
Flight Mass Spectrometry ◽  
Similar Weight ◽  
Underlying Mechanisms ◽  
Landes Geese ◽  
Tof Ms

During the process of fatty liver production by overfeeding, the levels of endogenous metabolites in the serum of geese would change dramatically. This study investigated the effects of overfeeding on serum metabolism of Landes geese and the underlying mechanisms using a metabolomics approach. Sixty Landes geese of the same age were randomly divided into the following three groups with 20 replicates in each group: D0 group (free from gavage); D7 group (overfeeding for 7 days); D25 group (overfeeding for 25 days). At the end of the experiment, 10 geese of similar weight from each group were selected for slaughter and sampling. The results showed that overfeeding significantly increased the body weight and the liver weight of geese. Serum enzymatic activities and serum lipid levels were significantly enhanced following overfeeding. Gas chromatography time-of-flight/mass spectrometry (GC-TOF/MS) was employed to explore the serum metabolic patterns, and to identify potential contributors to the formation of fatty liver and the correlated metabolic pathways. Relative to overfeeding for 7 days, a large number of endogenous molecules in serum of geese overfed for 25 days were altered. Continuous elevated levels of pyruvic acid, alanine, proline and beta-glycerophosphoric acid and reduced lactic acid level were observed in the serum of overfed geese. Pathway exploration found that the most of significantly different metabolites were involved in amino acids, carbohydrate and lipid metabolism. The present study exhibited the efficient capability of Landes geese to produce fatty liver, identified potential biomarkers and disturbed metabolic pathways in liver steatosis. These findings might reveal the underlying mechanisms of fatty liver formation and provide some theoretical basis for the diagnosis and treatment of liver diseases.

Comparative proteomic analysis on human L-02 liver cells treated with varying concentrations of trichloroethylene

2007 ◽  
Vol 23 (2) ◽  
pp. 91-101 ◽  
Author(s):  
Jianjun Liu ◽  
Haiyan Huang ◽  
Xiumei Xing ◽  
Renrong Xi ◽  
Zhixiong Zhuang ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Underlying Mechanism ◽  
Liver Cells ◽  
Control Group ◽  
Two Dimensional Gel Electrophoresis ◽  
Comparative Proteomic Analysis ◽  
Maldi Tof ◽  
Flight Mass Spectrometry ◽  
Peptide Mass ◽  
Tof Ms

To determine the differential proteomic expressions in human L-02 liver cells induced by varying concentrations of trichloroethylene (TCE), comparative proteomic analysis was performed on human L-02 liver cells which were treated with varying concentrations of TCE. According to the result of MTT test, we designed four different groups, in which the cells were treated with 0 μM (control group), 3, 10 or 40 μM TCE for 24 h, respectively. Comparative analysis of approximately 800 spots resolved by two-dimensional gel electrophoresis (2DE) in the soluble proteomes of L-02 cells from the four different groups resulted in 10 differential proteins. To identify the differential spots, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) was carried out; if the results from the tool were insufficient, tandem MS (MALDI-TOF-TOF-MS) was then performed. The raw data of peptide mass fingerprints (PMFs) and MS/MS spectra were searched against the IPI human data base for exact matches. Then western blot was employed to verify the result of proteomic analysis, the following result confirmed that the results of proteomic analysis were reliable. These results might provide an insight into the underlying mechanism of TCE intoxication and find biological markers for diagnosis and therapy of TCE-induced diseases.

scholarly journals Urine metabolomics of rats with chronic atrophic gastritis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0236203
Author(s):  
Guo-Xiu Zu ◽  
Qian-Qian Sun ◽  
Jian Chen ◽  
Xi-Jian Liu ◽  
Ke-Yun Sun ◽  
...  
Keyword(s):  
Atrophic Gastritis ◽  
Metabolic Pathways ◽  
Wistar Rats ◽  
Acid Metabolism ◽  
Chronic Atrophic Gastritis ◽  
Control Group ◽  
Liquid Chromatography Mass Spectrometry ◽  
Model Group ◽  
Rat Urine ◽  
Pathological Model

Background/aim To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG). Materials and methods Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method. Results Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism. Conclusion By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.

scholarly journals UPLC Q-TOF/MS-Based Metabolic Profiling of Urine Reveals the Novel Antipyretic Mechanisms of Qingkailing Injection in a Rat Model of Yeast-Induced Pyrexia

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoyan Gao ◽  
Mingxing Guo ◽  
Long Peng ◽  
Baosheng Zhao ◽  
Jiankun Su ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Ultra Performance Liquid Chromatography ◽  
Control Group ◽  
The Novel ◽  
Model Group ◽  
Antipyretic Effect ◽  
Flight Mass Spectrometry ◽  
Pharmacological Method ◽  
Clinical Emergency ◽  
Tof Ms

Fever is one of the most common clinical symptoms of many diseases. Qingkailing (QKL) injection is widely used in China as a clinical emergency medicine due to its good antipyretic effects. It is a herbal formula which is composed by eight kinds of traditional Chinese medicines (TCM). As a kind of typical multiple constituents and multiple actions of TCM, it is very difficult to elaborate the antipyretic mechanism by conventional pharmacological method. Metabonomics technique provides beneficial tool for this challenge. In this study, an ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS) metabonomics method was developed to explore the changing process of biochemical substances in rats of yeast-induced pyrexia. Partial least squares discriminate analysis (PLS-DA) was used to distinguish the normal control group, the pyrexia model group, and the pyrexia model group treated by QKL injection. The potential biomarkers related to pyrexia were confirmed and identified. MetPA was used to find the possible metabolic pathways. The results indicated that the antipyretic effect of QKL injection on yeast-induced pyrexia rats was performed by repairing the perturbed metabolism of amino acids.

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