Serum metabolic fingerprinting after exposure of rats to quinolinic acid.
Quinolinic acid (QUIN), one of the end metabolites in the kynurenine pathway, plays an important role in the pathogenesis of several diseases. Serum QUIN concentration rises in patients with renal dysfunction, liver cirrhosis, and many other inflammatory diseases. In the present study, osmotic minipumps containing QUIN (0.3 and 1mg/day) were implanted intraperitoneally into rats for 28days. Then, the physiological and toxicological variables were evaluated and LC-QTOF-MS serum metabolic fingerprinting was performed. QUIN significantly decreased the serum concentrations of several amino acids (phenylalanine, valine, tyrosine, and tryptophan), pantothenic acid, branched chain C4 acylcarnitine, total cholesterol, and glucose; increased the serum concentrations of amides (pentadecanoic amide, palmitic amide, oleamide, and stearamide), polyamines (spermine and spermidine), sphingosine, and deoxy-prostaglandin; caused alterations in phospholipids. This is the first report of comprehensive metabolites analysis after chronic intraperitoneal administration of QUIN. Further studies could develop new therapeutics for patients with disorders accompanied by increased serum level of QUIN.
Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland. Electronic address: kalaskab@gmail.com.
Bartlomiej
B
Kalaska
Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
Michal
M
Ciborowski
Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland.
Tomasz
T
Domaniewski
Department of Pharmaceutical Analysis, Medical University of Bialystok, Bialystok, Poland.
Urszula
U
Czyzewska
CEMBIO, Centre for Metabolomics and Bioanalysis, San Pablo CEU University, Boadilla del Monte, Spain.
Joanna
J
Godzien
Department of Pharmaceutical Analysis, Medical University of Bialystok, Bialystok, Poland.
Wojciech
W
Miltyk
Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
Adam
A
Kretowski
Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.
Dariusz
D
Pawlak
D000818:Animals; D007260:Infusion Pumps; D007263:Infusions, Parenteral; D008297:Male; D055432:Metabolomics; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats
D017378:Quinolinic Acid
Biochemistry; LC–MS; Metabolic fingerprinting; Metabolomics; Quinolinic acid