scholarly journals Pharmacokinetic and Metabolomic Studies with BIO 300, a Nanosuspension of Genistein, in a Nonhuman Primate Model

2019 ◽  
Vol 20 (5) ◽  
pp. 1231 ◽  
Author(s):  
Amrita Cheema ◽  
Khyati Mehta ◽  
Paola Santiago ◽  
Oluseyi Fatanmi ◽  
Michael Kaytor ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Metabolite Profile ◽  
Ultra Performance Liquid Chromatography ◽  
Acute Radiation ◽  
Initial Assessment ◽  
Serum Samples ◽  
Primate Model ◽  
Delayed Effects ◽  
Flight Mass Spectrometry ◽  
Drug Ingredient

Genistein is a naturally occurring phytoestrogen isoflavone and is the active drug ingredient in BIO 300, a radiation countermeasure under advanced development for acute radiation syndrome (H-ARS) and for the delayed effects of acute radiation exposure (DEARE). Here we have assessed the pharmacokinetics (PK) and safety of BIO 300 in the nonhuman primate (NHP). In addition, we analyzed serum samples from animals receiving a single dose of BIO 300 for global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS). We present a comparison of how either intramuscularly (im) or orally (po) administered BIO 300 changed the metabolomic profile. We observed transient alterations in phenylalanine, tyrosine, glycerophosphocholine, and glycerophosphoserine which reverted back to near-normal levels 7 days after drug administration. We found a significant overlap in the metabolite profile changes induced by each route of administration; with the po route showing fewer metabolic alterations. Taken together, our results suggest that the administration of BIO 300 results in metabolic shifts that could provide an overall advantage to combat radiation injury. This initial assessment also highlights the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of BIO 300.

scholarly journals Comparative proteomic analysis of serum from nonhuman primates administered BIO 300: a promising radiation countermeasure

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Michael Girgis ◽  
Yaoxiang Li ◽  
Junfeng Ma ◽  
Miloslav Sanda ◽  
Stephen Y. Wise ◽  
...  
Keyword(s):  
Drug Administration ◽  
Nonhuman Primates ◽  
Serum Proteins ◽  
Ultra Performance Liquid Chromatography ◽  
Acute Radiation ◽  
Delayed Effects ◽  
Routes Of Administration ◽  
Protein Levels ◽  
Flight Mass Spectrometry ◽  
Routes Of Drug Administration

Abstract Hematopoietic acute radiation syndrome (H-ARS) and delayed effects of acute radiation exposure (DEARE) are detrimental health effects that occur after exposure to high doses of ionizing radiation. BIO 300, a synthetic genistein nanosuspension, was previously proven safe and effective against H-ARS when administered (via the oral (po) or intramuscular (im) route) prior to exposure to lethal doses of total-body radiation. In this study, we evaluated the proteomic changes in serum of nonhuman primates (NHP) after administering BIO 300 by different routes (po and im). We utilized nanoflow-ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (NanoUPLC-MS/MS) methods for comprehensive global profiling and quantification of serum proteins. The results corroborate previous findings that suggest a very similar metabolic profile following both routes of drug administration. Furthermore, we observed minor alterations in protein levels, 2 hours after drug administration, which relates to the Cmax of BIO 300 for both routes of administration. Taken together, this assessment may provide an insight into the mechanism of radioprotection of BIO 300 and a reasonable illustration of the pharmacodynamics of this radiation countermeasure.

scholarly journals Acylated Flavonoid Glycosides are the Main Pigments that Determine the Flower Colour of the Brazilian Native Tree Tibouchina pulchra (Cham.) Cogn.

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 718 ◽  
Author(s):  
Fernanda Rezende ◽  
Marcelo Ferreira ◽  
Mads Clausen ◽  
Magdalena Rossi ◽  
Claudia Furlan
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Flower Colour ◽  
Metabolite Profile ◽  
Ultra Performance Liquid Chromatography ◽  
Flavonoid Glycosides ◽  
Array Detector ◽  
Flight Mass Spectrometry ◽  
Photodiode Array Detector ◽  
Photodiode Array

Tibouchina pulchra (Cham.) Cogn. is a plant native to Brazil whose genus and family (Melastomataceae) are poorly studied with regards to its metabolite profile. Phenolic pigments of pink flowers were studied by ultra-performance liquid chromatography with a photodiode array detector and electrospray ionization quadrupole time-of-flight mass spectrometry. Therein, twenty-three flavonoids were identified with eight flavonols isolated by preparative high-performance liquid chromatography and analysed by one- and two-dimensional nuclear magnetic resonance. Kaempferol derivatives were the main flavonols, encompassing almost half of the detected compounds with different substitution patterns, such as glucoside, pentosides, galloyl-glucoside, p-coumaroyl-glucoside, and glucuronide. Concerning the anthocyanins, petunidin p-coumaroyl-hexoside acetylpentoside and malvidin p-coumaroyl-hexoside acetylpentoside were identified and agreed with previous reports on acylated anthocyanins from Melastomataceae. A new kaempferol glucoside was identified as kaempferol-(2′′-O-methyl)-4′-O-α-d-glucopyranoside. Moreover, twelve compounds were described for the first time in the genus with five being new to the family, contributing to the chemical characterisation of these taxa.

scholarly journals A Nonhuman Primate Model of the Hematopoietic Acute Radiation Syndrome Plus Medical Management

2012 ◽  
Vol 103 (4) ◽  
pp. 367-382 ◽  
Author(s):  
Ann M. Farese ◽  
Melanie V. Cohen ◽  
Barry P. Katz ◽  
Cassandra P. Smith ◽  
William Jackson ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Medical Management ◽  
Acute Radiation ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Acute Radiation Syndrome

scholarly journals Obesity-Related Metabolomic Analysis of Human Subjects in Black Soybean Peptide Intervention Study by Ultraperformance Liquid Chromatography and Quadrupole-Time-of-Flight Mass Spectrometry

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Min Jung Kim ◽  
Hye Jeong Yang ◽  
Jin Hee Kim ◽  
Chang-Won Ahn ◽  
Jong Ho Lee ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Dietary Intervention ◽  
Human Subjects ◽  
Time Of Flight ◽  
Test Group ◽  
Ultra Performance Liquid Chromatography ◽  
Serum Samples ◽  
Black Soybean ◽  
Flight Mass Spectrometry

The present study aimed to identify key metabolites related to weight reduction in humans by studying the metabolic profiles of sera obtained from 34 participants who underwent dietary intervention with black soybean peptides (BSP) for 12 weeks. This research is a sequel to our previous work in which the effects of BSP on BMI and blood composition of lipid were investigated. Sera of the study were subjected to ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and the data were analyzed using partial least-squares discriminate analysis (PLS-DA) score plots. Body mass index and percent body fat of the test group were reduced. Levels of betaine, benzoic acid, pyroglutamic acid, pipecolic acid,N-phenylacetamide, uric acid,l-aspartyl-l-phenylalanine, and lysophosphatidyl cholines (lysoPCs) (C18:1, C18:2, C20:1, and C20:4) showed significant increases. Levels ofl-proline, valine,l-leucine/isoleucine, hypoxanthine, glutamine,l-methionine, phenylpyruvic acid, several carnitine derivatives, and lysoPCs (C14:0, PC16:0, C15:0, C16:0, C17:1, C18:0, and C22:0) were significantly decreased. In particular, lysoPC 16:0 with a VIP value of 12.02 is esteemed to be the most important metabolite for evaluating the differences between the 2 serum samples. Our result confirmed weight-lowering effects of BSP, accompanied by favorable changes in metabolites in the subjects’ blood. Therefore, this research enables us to better understand obesity and increases the predictability of the obesity-related risk by studying metabolites present in the blood.

Maternal High-Fat Diet Persistently Alters Bone Marrow Immune Cell Proportions and Function in a Nonhuman Primate Model

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 222-OR
Author(s):  
MICHAEL J. NASH ◽  
TAYLOR K. SODERBORG ◽  
RACHEL C. JANSSEN ◽  
ERIC M. PIETRAS ◽  
JACOB E. FRIEDMAN
Keyword(s):  
Bone Marrow ◽  
Nonhuman Primate ◽  
High Fat Diet ◽  
Immune Cell ◽  
High Fat ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
And Function
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