Recent Trends in the Quantification of Biogenic Amines in Biofluids
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Journal of Clinical Medicine Review Recent Trends in the Quantification of Biogenic Amines in Biofluids as Biomarkers of Various Disorders: A Review Alina Plenis 1,* , Ilona Ol˛edzka 1 , Piotr Kowalski 1 , Natalia Mi˛ekus 1,2 and Tomasz B ˛aczek 1 1 Department of Pharmaceutical Chemistry, Medical University of Gda´nsk,Hallera 107, 80-416 Gda´nsk, Poland; [email protected] (I.O.); [email protected] (P.K.); [email protected] (N.M.); [email protected] (T.B.) 2 Department of Animal and Human Physiology, Faculty of Biology, University of Gda´nsk,Wita Stwosza 59, 80-308 Gda´nsk,Poland * Correspondence: [email protected]; Fax: +48-58-349-16-35 Received: 4 April 2019; Accepted: 6 May 2019; Published: 9 May 2019 Abstract: Biogenic amines (BAs) are bioactive endogenous compounds which play a significant physiological role in many cell processes like cell proliferation and differentiation, signal transduction and membrane stability. Likewise, they are important in the regulation of body temperature, the increase/decrease of blood pressure or intake of nutrition, as well as in the synthesis of nucleic acids and proteins, hormones and alkaloids. Additionally, it was confirmed that these compounds can be considered as useful biomarkers for the diagnosis, therapy and prognosis of several neuroendocrine and cardiovascular disorders, including neuroendocrine tumours (NET), schizophrenia and Parkinson’s Disease. Due to the fact that BAs are chemically unstable, light-sensitive and possess a high tendency for spontaneous oxidation and decomposition at high pH values, their determination is a real challenge. Moreover, their concentrations in biological matrices are extremely low. These issues make the measurement of BA levels in biological matrices problematic and the application of reliable bioanalytical methods for the extraction and determination of these molecules is needed. This article presents an overview of the most recent trends in the quantification of BAs in human samples with a special focus on liquid chromatography (LC), gas chromatography (GC) and capillary electrophoresis (CE) techniques. Thus, new approaches and technical possibilities applied in these methodologies for the assessment of BA profiles in human samples and the priorities for future research are reported and critically discussed. Moreover, the most important applications of LC, GC and CE in pharmacology, psychology, oncology and clinical endocrinology in the area of the analysis of BAs for the diagnosis, follow-up and monitoring of the therapy of various health disorders are presented and critically evaluated. Keywords: biogenic amines; biomarkers; human samples; liquid chromatography; gas chromatography; capillary electrophoresis; non-separation techniques 1. Introduction The unbalanced secretion and elimination of pivotal biogenic amines (BAs) (such as serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (E)) can have severe health consequences since they act not only as neurotransmitters but take part in the regulation of mood, sleep, immune response, thermoregulation and cardiovascular and gut functions, among others [1]. To start with, in the diagnosis and monitoring of central nervous system (CNS) pathologies, such as neurodegenerative disorders, levels of BAs and their main metabolites in body fluids differentiated the healthy persons from the patients with Alzheimer’s Disease (AD) [2]. J. Clin. Med. 2019, 8, 640; doi:10.3390/jcm8050640 www.mdpi.com/journal/jcm J. Clin. Med. 2019, 8, 640 2 of 55 J. Clin. Med. 2019, 8, x FOR PEER REVIEW 2 of 58 Also, changes in the central noradrenergic, serotonergic and dopaminergic neurotransmitter systems werehealthy demonstrated persons from to play the apatients relevant with role inAlzheimer’ the behaviourals Disease and (AD) psychological [2]. Also, changes signs and in symptoms the central of dementianoradrenergic, manifestation serotonergic [3]. and Other dopaminergic studies revealed neurotransmitter that not only systems must were dopaminergic demonstrated transmission to play a berelevant monitored role in for the Parkinson’s behavioural Disease and psychological (PD) but also signs non-DA and symptoms neurotransmitter of dementia systems manifestation in the brain [3]. areOther significantly studies revealed desynchronized that not only in PD, must as welldopami as thenergic interaction transmission between be monitored the different for Parkinson’s BA systems, whichDisease contributes (PD) but also to thenon-DA development neurotransmitter of the manifestationssystems in the brain of PD are [ 4significantly]. Neuroendocrine desynchronized system pathologiesin PD, as well might as the be interaction diagnosed between and monitored the different through BA systems, the determination which contributes of BAs, to the for development example: the diagnosisof the manifestations of catecholamine-producing of PD [4]. Neuroendocrine neuroendocrine system patholog tumoursies (NETs): might be pheochromocytoma diagnosed and monitored (PHE) andthrough neuroblastoma the determination (NB), is supported of BAs, byfor the example: determination the diagnosis of BAs inof patients’ catecholamine-producing body fluids (urine, plasma,neuroendocrine serum) and tumours indoleamine-producing (NETs): pheochromocytoma NETs–carcinoids–could (PHE) and neuroblastoma be diagnosed (NB), via isdiscriminating supported by thethe level determination of 5-hydroxyindoleacetic of BAs in patients’ acid body (5-HIAA)–the fluids (urine, main plasma, serotonin serum) metabolite–in and indoleamine-producing patients’ 24-hour urineNETs–carcinoids–could samples [5]. be diagnosed via discriminating the level of 5-hydroxyindoleacetic acid (5- HIAA)–theFrom the main L-Tryptophan serotonin metabolite–in (L-Tryp) metabolic patients’ pathway, 24-hour thoseurine samples analytical [5]. approaches should also be From the L-Tryptophan (L-Tryp) metabolic pathway, those analytical approaches should also be able to determine at least 5-HT and 5-HIAA in biological samples. L-Tryp is a neutral, essential amino able to determine at least 5-HT and 5-HIAA in biological samples. L-Tryp is a neutral, essential amino acid and it is the only amino acid in proteins derived from indole, a bicyclic ring formed by a benzene acid and it is the only amino acid in proteins derived from indole, a bicyclic ring formed by a benzene and a pyrrole group. The L-Tryp indole ring in –R residues assists the stabilization of protein and and a pyrrole group. The L-Tryp indole ring in –R residues assists the stabilization of protein and peptide structures and allows their interactions through Van der Waals forces, whereas the indole ring peptide structures and allows their interactions through Van der Waals forces, whereas the indole ring inin –N –N residues residues demonstratesdemonstrates susceptibility susceptibility as as a hydr a hydrogenogen bond bond donor, donor, which which could could also alsoexplain explain the role the roleof L-Tryp of L-Tryp in protein in protein binding binding and recognition. and recognition. Furthermore, Furthermore, L-Tryp L-Trypis an essential is an essential precursor precursor of various of variousbioactive bioactive compounds compounds such as suchkynurenines as kynurenines and serotoni and serotoninn (5-HT) (Figure (5-HT) 1). (Figure L-Tryp1). is L-Tryp converted is converted to 5-HT toby 5-HT enzymes by enzymes in intestinal in intestinal and nervous and nervoustissue. Only tissue. a very Only small a very amount small of amountdietary L-Tryp of dietary is converted L-Tryp is convertedinto 5-HT into and 5-HT about and 90% about of L-Tryp 90%of biotransformation L-Tryp biotransformation consists of consists the breaking of the of breaking the indole of thering indole and ringturn and over turn into over the kynurenine into the kynurenine (KYN) pathway (KYN) and pathway nicotinic and acid nicotinic (NU). acid (NU). FigureFigure 1. 1.The The mainmain productsproducts of the L-Tryp metabolic metabolic pathway. pathway. AA studystudy ofof thethe basic biology biology of of the the L-Tryp L-Tryp me metabolismtabolism pointed pointed out outthe therelevant relevant issue issue of the of thebioavailability bioavailability of this of amino this amino acid or acid changes or changes in the regulation in the regulation of its metabolism of its metabolism in tissues. Therefore, in tissues. Therefore,studying studyingthe unbalanced the unbalanced transformation transformation of this am ofino this acid amino during acid the during pathological the pathological stages of stages the oforganism the organism is relevant. is relevant. Serotonin Serotonin synthesis synthesis occurs occurs in the in theperiphery periphery within within the the gut gut neurons neurons and and enterochromaenterochromaffinffin cells cells and and inin thethe centralcentral nervousnervous systemsystem within the neurons of of the the raphe raphe in in the the brain brain stem.stem. L-Tryp L-Tryp is is hydroxylated hydroxylated to to 5-hydroxytryptophan5-hydroxytryptophan (5-HTrp) by the enzyme tryptophan tryptophan hydroxylase hydroxylase type 2, the rate limiting step in brain serotonin synthesis. Furthermore, decarboxylation, via the J. Clin. Med. 2019, 8, x FOR PEER REVIEW 3 of 58 J. Clin. Med. 2019, 8, 640 3 of 55 type 2, the rate limiting step in brain serotonin synthesis. Furthermore, decarboxylation, via the enzymaticenzymatic action action of of the the L-aromatic L-aromatic acid acid decarboxylase, decarboxylase, occurred occurred leading