Targeting the Lowest Concentration of a Toxin that Induces a Detectable Metabolic Response in living Organisms: Time Resolved In vivo 2D NMR During a Concentration Ramp.
 

Targeting the Lowest Concentration of a Toxin that Induces a Detectable Metabolic Response in living Organisms: Time Resolved In vivo 2D NMR During a Concentration Ramp.

Related Articles Targeting the Lowest Concentration of a Toxin that Induces a Detectable Metabolic Response in living Organisms: Time Resolved In vivo 2D NMR During a Concentration Ramp.

Anal Chem. 2020 Jun 18;:

Authors: Lane D, Bermel W, Ning P, Jeong TY, Martin R, Soong R, Wu B, Tabatabaei-Anaraki M, Heumann H, Gundy M, Boenisch H, Adamo A, Arhonditsis GB, Simpson AJ

Abstract
In vivo Nuclear Magnetic Resonance (NMR) is a powerful analytical tool for probing complex biological processes inside living organisms. However, due to magnetic susceptibility broadening, which produces broad lines in 1D NMR, 1H-13C 2D NMR is required for metabolite monitoring in vivo. As each 2D experiment is time consuming, often hours, this limits the temporal resolution over which in vivo processes can be monitored. Furthermore, to understand concentration dependent responses, studies are traditionally repeated using different contaminant/toxin concentrations, which can make studies prohibitively long (potentially months). In the present study, time resolved non-uniform sampling NMR is performed in the presence of a contaminant concentration sweep. The result is that the lowest concentration that elicits a metabolic response can be rapidly detected, while the metabolic pathways impacted provide information as to the toxic mode-of-action of the toxin. The lowest concentration of bisphenol A (BPA) that induces a response was ~ 0.1mg/L (detected in just 16 mins) while changes in different metabolites suggest a complex multi pathway response that leads to protein degradation at higher BPA concentrations. This proof of concept shows it is possible, based on "real-time" organism responses, to identify the sub-lethal concentration at which a toxin impacts an organism, and thus represents an essential analytical tool for the next generation of toxicity-based research and monitoring.


PMID: 32551506 [PubMed - as supplied by publisher]



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