Fishing for antidotes - - Chromatography Online
Fishing for antidotes

The Column
Volume 8, Issue 19

Organophosphates (OPs) are commonly found in commercial pesticides and are highly toxic to humans if inhaled or ingested, resulting in both behavioural and psychological symptoms. OPs chemically modify the essential protein acetylcholine esterase, which is principally responsible for the breakdown of the essential neurotransmitter acetylcholine.

A group of investigators in the USA1 have developed a novel assay using the model organism zebrafish (Danio rerio) for the screening of existing drug libraries to identify compounds effective in the treatment of OP poisoning.The investigators found that OP administration to zebrafish larvae induced similar symptoms to those seen in humans, followed by death. The investigators used the prototypical OP azinphos-methyl to screen 1200 known drugs in a 96-well plate format and demonstrated that 16 of the drugs screened have a protective effect on the zebrafish using a LC–MS–MS based metabolite profiling approach.

Acetylcholine is an essential neurotransmitter, acting as a chemical signal for the transmission of information across synapses in the brain, undergoing formation and breakdown cyclically. OPs act to block the breakdown of acetylcholine by blocking the action of the enzyme, acetylcholine esterase. This blocking action results in an unnatural accumulation of acetylcholine within the synapse, therefore inducing continuous firing of signals resulting in behavioural and psychological symptoms. The currently used antidote for OP poisoning is a combination of atropine and pralidoxime (2-PAM); however, there are unacceptable risks of increased blood pressure associated with treatment and so identifying new drugs is a priority.

The lead investigator of the study Dr Randall Peterson told The Column, “Humans are confronted by all sorts of toxic chemicals through both accidental and intentional exposures (such as chemotherapy). Our findings suggest that zebrafish could be used to systematically screen for antidotes that are protective against organophosphate exposure or virtually any other toxic chemical.”

1. S. Jin et al, Journal of Biomolecular Screening, DOI:10.1177/1087057112458153.

This story originally appeared in The Column. Click here to view that issue.

ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters
Global E-newsletters subscribe here:




 

LCGC COLUMNISTS 2014

Column Watch: Ron Majors, established authority on new column technologies, keeps readers up-to-date with new sample preparation trends in all branches of chromatography and reviews developments. LATEST: When Bad Things Happen to Good Food: Applications of HPLC to Detect Food Adulteration


Perspectives in Modern HPLC: Michael W. Dong is a senior scientist in Small Molecule Drug Discovery at Genentech in South San Francisco, California. He is responsible for new technologies, automation, and supporting late-stage research projects in small molecule analytical chemistry and QC of small molecule pharmaceutical sciences. LATEST: HPLC for Characterization and Quality Control of Therapeutic Monoclonal Antibodies


MS — The Practical Art: Kate Yu brings her expertise in the field of mass spectrometry and hyphenated techniques to the pages of LCGC. In this column she examines the mass spectrometric side of coupled liquid and gas-phase systems. Troubleshooting-style articles provide readers with invaluable advice for getting the most from their mass spectrometers. LATEST: Radical Mass Spectrometry as a New Frontier for Bioanalysis


LC Troubleshooting: LC Troubleshooting sets about making HPLC methods easier to master. By covering the basics of liquid chromatography separations and instrumentation, John Dolan is able to highlight common problems and provide remedies for them. LATEST: How Much Can I Inject? Part I: Injecting in Mobile Phase


More LCGC Columnists>>

LCGC North America Editorial Advisory Board>>

LCGC Europe Editorial Advisory Board>>

LCGC Editorial Team Contacts>>


Source: The Column,
Click here