Monitoring of kynurenine pathway metabolites, neurotransmitters and their metabolites in blood plasma and brain tissue of individuals with latent toxoplasmosis
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
30925271
DOI
10.1016/j.jpba.2019.03.039
PII: S0731-7085(18)32571-8
Knihovny.cz E-resources
- Keywords
- HPLC-ESI-MS/MS, Kynurenine catabolic pathway, Latent toxoplasmosis, Principal component analysis,
- MeSH
- Plasma metabolism MeSH
- Rats MeSH
- Kynurenine analogs & derivatives blood metabolism MeSH
- Quinolinic Acid blood metabolism MeSH
- Hydroxyindoleacetic Acid blood metabolism MeSH
- Brain metabolism MeSH
- Neurotransmitter Agents metabolism MeSH
- Rats, Wistar MeSH
- Serotonin metabolism MeSH
- Tandem Mass Spectrometry methods MeSH
- Toxoplasmosis blood metabolism MeSH
- Tryptophan metabolism MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 3-hydroxykynurenine MeSH Browser
- Kynurenine MeSH
- Quinolinic Acid MeSH
- Hydroxyindoleacetic Acid MeSH
- Neurotransmitter Agents MeSH
- Serotonin MeSH
- Tryptophan MeSH
The aim of the presented work was to develop a highly sensitive, accurate and rapid analytical method for the determination of concentration levels of tryptophan and its metabolites of kynurenine catabolic pathway, as well as neurotransmitters and their metabolites in complex biological matrices (brain tissue and blood plasma). The developed analytical method consists of analytes separation from the biological matrices by protein precipitation (blood plasma) or solvent extraction (brain tissue), derivatization of the analytes and their detection by high-performance liquid chromatography combined with mass spectrometry. Individual steps of the whole process were optimized and the method was validated in the terms of selectivity, linearity (R2≥0.980), precision (RSD ≤ 13.3%), recovery (≥82.0%), limit of detection (1.8 ng/mL of blood plasma, 2.2 pg/mg of brain tissue) and limit of quantification (2.5 ng/mL of blood plasma, 2.8 pg/mg of brain tissue). The method was subsequently verified by an animal study, where the concentration levels of the analytes in biological matrices (blood plasma and brain tissue) of T. gondii - infected rats and control animals were compared. All the data obtained from the animal study were statistically evaluated. Increased concentration levels of kynurenine catabolic pathway metabolites (e.g. kynurenine, 3-hydroxykynurenine, quinolinic acid) were observed in the case of T. gondii - infected rats in contrast to the control group. The opposite effect was determined in the case of serotonin and its metabolite 5-hydroxyindoleacetic acid, where higher concentration levels were found in blood plasma of healthy subjects. Finally, Principal Component Analysis (PCA) was utilized for a score plot formation. PCA score plots have demonstrated the similarities of individuals within each group and the differences among the groups.
3rd Faculty of Medicine Charles University Ruská 87 100 00 Prague 10 Czech Republic
National Institute of Mental Health Topolová 748 250 67 Klecany Czech Republic
The National Institute of Public Health Šrobárova 48 100 42 Prague 10 Czech Republic
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