Metabolomic Profiling of In Vivo Plasma Responses to Dioxin-Associated Dietary Contaminant Exposure in Rats: Implications for Identification of Sources of Animal and Human Exposure

2013 ◽  
Vol 47 (10) ◽  
pp. 5409-5418 ◽  
Author(s):  
Anthony A. O’Kane ◽  
Olivier P. Chevallier ◽  
Stewart F. Graham ◽  
Christopher T. Elliott ◽  
Mark H. Mooney
Keyword(s):  
Human Exposure ◽  
Contaminant Exposure ◽  
Metabolomic Profiling

scholarly journals Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yasaman Barekatain ◽  
Jeffrey J. Ackroyd ◽  
Victoria C. Yan ◽  
Sunada Khadka ◽  
Lin Wang ◽  
...  
Keyword(s):  
Clinical Relevance ◽  
Homozygous Deletion ◽  
In Vitro Models ◽  
Arginine Methyltransferase ◽  
Human Glioblastoma ◽  
Primary Glioblastoma ◽  
Methylthioadenosine Phosphorylase ◽  
Metabolomic Profiling

AbstractHomozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP’s substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate that homozygous MTAP-deleted primary glioblastoma tumors do not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma. These findings highlight metabolic discrepancies between in vitro models and primary human tumors that must be considered when developing strategies for precision therapies targeting glioblastoma with homozygous MTAP deletion.

scholarly journals Cardioprotective and Metabolomic Profiling of Selected Medicinal Plants against Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Nadia Afsheen ◽  
Khalil-ur-Rehman ◽  
Nazish Jahan ◽  
Misbah Ijaz ◽  
Asad Manzoor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Medicinal Plants ◽  
Plasmid Dna ◽  
Research Work ◽  
Antioxidant Potential ◽  
Piper Nigrum ◽  
Coronary Artery Ligation ◽  
Hemodynamic Parameters ◽  
Metabolomic Profiling

In this research work, the antioxidant and metabolomic profiling of seven selected medicinally important herbs including Rauvolfia serpentina, Terminalia arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and Crataegus oxyacantha was performed. The in vivo cardioprotective potential of these medicinal plants was evaluated against surgically induced oxidative stress through left anterior descending coronary artery ligation (LADCA) in dogs. The antioxidant profiling of these plants was done through DPPH and DNA protection assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential, while the E. cardamom showed poor antioxidative strength even at its high concentration. Different concentrations of extracts of the said plants exhibited the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA merely treated with H2O2. The metabolomic profiling through LC-MS analysis of these antioxidants revealed the presence of active secondary metabolites responsible for their antioxidant potential. During in vivo analysis, blood samples of all treatment groups were drawn at different time intervals to analyze the cardiac and hemodynamic parameters. The results depicted that the group pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as well as hemodynamic parameters near to normal. The histopathological examination also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe and inexpensive cardioprotective herbal combination could be considered as an alternate of synthetic drugs.

scholarly journals Histone Adduction with Nicotine: A Bio-Ams Study

Radiocarbon ◽  
1997 ◽  
Vol 39 (3) ◽  
pp. 293-297 ◽  
Author(s):  
X. H. Wu ◽  
H. F. Wang ◽  
Y. F. Liu ◽  
X. Y. Lu ◽  
J. J. Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Accelerator Mass Spectrometry ◽  
Human Exposure ◽  
Mouse Liver ◽  
Dose Range ◽  
The Other ◽  
Histone 3 ◽  
Protein Adduction ◽  
Dna Adduction

Based on the study of DNA adduction with nicotine, we have measured the mouse hepatic histone adduction with 14C-labeled nicotine in vivo by bio-accelerator mass spectrometry (bio-AMS). In the exposure of mice to nicotine, the dose range administered was from 0.2 μg to 6.0 μg kg b.w.-1, which was equivalent to a very low level of human exposure to cigarette smoke. The adducts of either histone 1 (H1) or histone 3 (H3) with nicotine in mouse liver increased markedly with increasing nicotine dose. Our results have demonstrated that in the study of protein adduction with toxic xenobiotics as a biomarker, the AMS method achieves the highest sensitivity, 4.6 × 10-17 mol (46 amol) adducts per mg H1 protein, compared to all the other methods used previously.

scholarly journals FSMP-17. GLOBAL METABOLOMIC PROFILING OF GLIOBLASTOMA MULTIFORME REVEALS METABOLIC VULNERABILITIES IN RESPONSE TO RADIATION THERAPY

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Aarooran Durairaj ◽  
Melanie McReynolds ◽  
Congcong Wang ◽  
Joy He ◽  
Joshua Rabinowitz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Glioblastoma Multiforme ◽  
Ionizing Radiation ◽  
Aminolevulinic Acid ◽  
Primary Brain Tumor ◽  
Metabolic Reprogramming ◽  
Pharmacological Intervention ◽  
Tumor Microenvironments ◽  
Metabolomic Profiling

Abstract Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, originates in astrocytes and oligodendrocytes and yields a median survival time of less than 2 years and a 5-year survival of 2.5%. There has been little in the way of treatments and novel approaches are needed to combat the poor prognosis of GBM. Recent studies have established that GBM cells exhibit metabolic reprogramming to adapt to diverse metabolic gradients within heterogenous tumor microenvironments. Using an unbiased metabolomics approach, we investigated metabolic changes both pre- and post-ionizing radiation across several patient-derived GBM cell lines. Surprisingly, acute high dosage of ionizing radiation resulted in significant changes in the synthesis of aminolevulinic acid (ALA), a non-proteinogenic amino acid. Fractionation of radiation therapy resulted in dose-dependent changes in the heme synthesis pathway within these cells. Using an orthotopic xenograft mouse model of GBM, we identify several enzymatic vulnerabilities in vivo and discuss a novel combinatorial therapeutic approach of radiation and targeted pharmacological intervention. Our findings reveal the fundamental biosynthetic changes that GBMs adopt when exposed to ionizing irradiation as well as the benefits of a combinatorial approach.

scholarly journals In Vitro and In Vivo Metabolomic Profiling after Infection with Virulent Newcastle Disease Virus

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 962 ◽  
Author(s):  
Panrao Liu ◽  
Yuncong Yin ◽  
Yabin Gong ◽  
Xusheng Qiu ◽  
Yingjie Sun ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
High Performance ◽  
Economic Losses ◽  
Viral Protein Synthesis ◽  
Metabolomic Profiling ◽  
Virulent Newcastle Disease Virus

Newcastle disease (ND) is an acute, febrile, highly contagious disease caused by the virulent Newcastle disease virus (vNDV). The disease causes serious economic losses to the poultry industry. However, the metabolic changes caused by vNDV infection remain unclear. The objective of this study was to determine the metabolomic profiling after infection with vNDV. DF-1 cells infected with the vNDV strain Herts/33 and the lungs from Herts/33-infected specific pathogen-free (SPF) chickens were analyzed via ultra-high-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) in combination with multivariate statistical analysis. A total of 305 metabolites were found to have changed significantly after Herts/33 infection, and most of them belong to the amino acid and nucleotide metabolic pathway. It is suggested that the increased pools of amino acids and nucleotides may benefit viral protein synthesis and genome amplification to promote NDV infection. Similar results were also confirmed in vivo. Identification of these metabolites will provide information to further understand the mechanism of vNDV replication and pathogenesis.

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