PUBLICATION

Comprehensive characterization of neurochemicals in three zebrafish chemical models of human acute organophosphorus poisoning using liquid chromatography-tandem mass spectrometry

Authors
Gómez-Canela, C., Tornero-Cañadas, D., Prats, E., Piña, B., Tauler, R., Raldúa, D.
ID
ZDB-PUB-180110-5
Date
2018
Source
Analytical and bioanalytical chemistry   410(6): 1735-1748 (Journal)
Registered Authors
Piña, Benjamin, Raldúa, Demetrio
Keywords
Acute organophosphorus poisoning, Animal models of human disease, LC-MS/MS, Neurotransmitters, Quality parameters, Zebrafish larvae
MeSH Terms
  • Acetylcholine/analysis
  • Acetylcholine/metabolism
  • Animals
  • Chromatography, High Pressure Liquid/methods*
  • Disease Models, Animal
  • Dopamine/analysis
  • Dopamine/metabolism
  • Epinephrine/analysis
  • Epinephrine/metabolism
  • Glutamic Acid/analysis
  • Glutamic Acid/metabolism
  • Glycine/analysis
  • Glycine/metabolism
  • Histamine/analysis
  • Histamine/metabolism
  • Humans
  • Neurotransmitter Agents/analysis
  • Neurotransmitter Agents/metabolism
  • Norepinephrine/analysis
  • Norepinephrine/metabolism
  • Organophosphate Poisoning/diagnosis*
  • Organophosphate Poisoning/metabolism
  • Serotonin/analysis
  • Serotonin/metabolism
  • Tandem Mass Spectrometry/methods*
  • Zebrafish*/metabolism
  • gamma-Aminobutyric Acid/analysis
  • gamma-Aminobutyric Acid/metabolism
PubMed
29313079 Full text @ Anal. Bioanal. Chem.
Abstract
There is a growing interest in biological models to investigate the effect of neurotransmitter dysregulation on the structure and function of the central nervous system (CNS) at different stages of development. Zebrafish, a vertebrate model increasingly used in neurobiology and neurotoxicology, shares the common neurotransmitter systems with mammals, including glutamate, GABA, glycine, dopamine, norepinephrine, epinephrine, serotonin, acetylcholine, and histamine. In this study, we have evaluated the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the multiresidue determination of neurotransmitters and related metabolites. In a first step, ionization conditions were tested in positive electrospray mode and optimum fragmentation patterns were determined to optimize two selected reaction monitoring (SRM) transitions. Chromatographic conditions were optimized considering the chemical structure and chromatographic behavior of the analyzed compounds. The best performance was obtained with a Synergy Polar-RP column, which allowed the separation of the 38 compounds in 30 min. In addition, the performance of LC-MS/MS was studied in terms of linearity, sensitivity, intra- and inter-day precision, and overall robustness. The developed analytical method was able to quantify 27 of these neurochemicals in zebrafish chemical models for mild (P1), moderate (P2), and severe (P3) acute organophosphorus poisoning (OPP). The results show a general depression of synaptic-related neurochemicals, including the excitatory and inhibitory amino acids, as well as altered phospholipid metabolism, with specific neurochemical profiles associated to the different grades of severity. These results confirmed that the developed analytical method is a new tool for neurotoxicology research using the zebrafish model.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping