scholarly journals A New Insight on the Radioprotective Potential of Epsilon-Aminocaproic Acid

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 663
Author(s):  
Timur Saliev ◽  
Dinara Baiskhanova ◽  
Dmitriy Beznosko ◽  
Dinara Begimbetova ◽  
Bauyrzhan Umbayev ◽  
...  
Keyword(s):  
Low Dose ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Aminocaproic Acid ◽  
Free Radical Scavengers ◽  
Peripheral Blood Mononuclear ◽  
X Ray ◽  
Radiation Induced ◽  
Induced Apoptosis ◽  
Epsilon Aminocaproic Acid

Background and objectives: The aim of the study was to scrutinize the ability of epsilon-aminocaproic acid (EACA) to prevent radiation-induced damage to human cells. Materials and Methods: Human peripheral blood mononuclear cells (PBMCs) were exposed to ionizing radiation at three low doses (22.62 mGy, 45.27 mGy, and 67.88 mGy) in the presence of EACA at the concentration of 50 ng/mL. Results: EACA was able to prevent cell death induced by low-dose X-ray radiation and suppress the formation of reactive oxygen species (ROS). EACA also demonstrated a capacity to protect DNA from radiation-induced damage. The data indicated that EACA is capable of suppression of radiation-induced apoptosis. Comparative tests of antioxidative activity of EACA and a range of free radical scavengers showed an ability of EACA to effectively inhibit the generation of ROS. Conclusions: This study showed that the pretreatment of PBMCs with EACA is able to protect the cells from radiation-elicited damage, including free radicals’ formation, DNA damage, and apoptosis.

scholarly journals Targeted Mass Spectrometry Enables Quantification of Novel Pharmacodynamic Biomarkers of ATM Kinase Inhibition

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3843
Author(s):  
Jeffrey R. Whiteaker ◽  
Tao Wang ◽  
Lei Zhao ◽  
Regine M. Schoenherr ◽  
Jacob J. Kennedy ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Limit Of Quantification ◽  
Peripheral Blood Mononuclear ◽  
Atm Kinase ◽  
Support Mechanism ◽  
Radiation Induced ◽  
Pharmacodynamic Biomarkers ◽  
Preclinical And Clinical Studies

The ATM serine/threonine kinase (HGNC: ATM) is involved in initiation of repair of DNA double-stranded breaks, and ATM inhibitors are currently being tested as anti-cancer agents in clinical trials, where pharmacodynamic (PD) assays are crucial to help guide dose and scheduling and support mechanism of action studies. To identify and quantify PD biomarkers of ATM inhibition, we developed and analytically validated a 51-plex assay (DDR-2) quantifying protein expression and DNA damage-responsive phosphorylation. The median lower limit of quantification was 1.28 fmol, the linear range was over 3 orders of magnitude, the median inter-assay variability was 11% CV, and 86% of peptides were stable for storage prior to analysis. Use of the assay was demonstrated to quantify signaling following ionizing radiation-induced DNA damage in both immortalized lymphoblast cell lines and primary human peripheral blood mononuclear cells, identifying PD biomarkers for ATM inhibition to support preclinical and clinical studies.

scholarly journals Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using gene expression whole genome microarrays

Genomics ◽  
2010 ◽  
Vol 96 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Saliha Yilmaz ◽  
Marta Boffito ◽  
Sophie Collot-Teixeira ◽  
Ferruccio De Lorenzo ◽  
Laura Waters ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Low Dose ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Whole Genome ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells
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