scholarly journals Coordination Complex Formation and Redox Properties of Kynurenic and Xanthurenic Acid Can Affect Brain Tissue Homeodynamics

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 476 ◽  
Author(s):  
Lenka Kubicova ◽  
Franz Hadacek ◽  
Gert Bachmann ◽  
Wolfram Weckwerth ◽  
Vladimir Chobot
Keyword(s):  
Complex Formation ◽  
Neurodegenerative Diseases ◽  
Antioxidant Activities ◽  
Differential Pulse ◽  
Coordination Complexes ◽  
Kynurenine Pathway ◽  
Coordination Complex ◽  
Xanthurenic Acid ◽  
Ros Scavenging ◽  
Deoxyribose Degradation

Reactive oxygen species (ROS) are known for their participation in various physiological and pathological processes in organisms, including ageing or degeneration. Kynurenine pathway metabolites, such as kynurenic (KYNA) or xanthurenic (XA) acid, can affect neurodegenerative diseases due to their ROS scavenging and Fe ion coordination complex formation but insights are still incomplete. Therefore, we investigated the formation and antioxidant capabilities of KYNA– and XA–Fe complexes by nano-electrospray−mass spectrometry, differential pulse voltammetry, deoxyribose degradation and FeII autoxidation assays. XA formed coordination complexes with FeII or FeIII ions and was an effective antioxidant. By contrast, only FeII–KYNA complexes could be detected. Moreover, KYNA showed no antioxidant effects in the FeCl3/ascorbic acid deoxyribose degradation assay variant and only negligible activities in the FeII autoxidation assay. Coordination complexes of Fe ions with KYNA probably stabilize KYNA in its keto tautomer form. Nevertheless, both KYNA and XA exhibited sufficient antioxidant activities in some of the employed assay variants. The results provide evidence that both have the potential to alleviate neurodegenerative diseases by helping to maintain tissue redox homeodynamics.

scholarly journals Natural Molecules and Neuroprotection: Kynurenic Acid, Pantethine and α-Lipoic Acid

2021 ◽  
Vol 22 (1) ◽  
pp. 403
Author(s):  
Fanni Tóth ◽  
Edina Katalin Cseh ◽  
László Vécsei
Keyword(s):  
Neurodegenerative Diseases ◽  
Lipoic Acid ◽  
Kynurenic Acid ◽  
Biological Activities ◽  
Neuroprotective Effect ◽  
Structural Diversity ◽  
Kynurenine Pathway ◽  
Glutamate Excitotoxicity ◽  
Neuroprotective Agents ◽  
Starting Point

The incidence of neurodegenerative diseases has increased greatly worldwide due to the rise in life expectancy. In spite of notable development in the understanding of these disorders, there has been limited success in the development of neuroprotective agents that can slow the progression of the disease and prevent neuronal death. Some natural products and molecules are very promising neuroprotective agents because of their structural diversity and wide variety of biological activities. In addition to their neuroprotective effect, they are known for their antioxidant, anti-inflammatory and antiapoptotic effects and often serve as a starting point for drug discovery. In this review, the following natural molecules are discussed: firstly, kynurenic acid, the main neuroprotective agent formed via the kynurenine pathway of tryptophan metabolism, as it is known mainly for its role in glutamate excitotoxicity, secondly, the dietary supplement pantethine, that is many sided, well tolerated and safe, and the third molecule, α-lipoic acid is a universal antioxidant. As a conclusion, because of their beneficial properties, these molecules are potential candidates for neuroprotective therapies suitable in managing neurodegenerative diseases.

scholarly journals Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Bernadett Tuka ◽  
Aliz Nyári ◽  
Edina Katalin Cseh ◽  
Tamás Körtési ◽  
Dániel Veréb ◽  
...  
Keyword(s):  
Anthranilic Acid ◽  
Clinical Relevance ◽  
Kynurenic Acid ◽  
Picolinic Acid ◽  
Plasma Concentrations ◽  
Episodic Migraine ◽  
Kynurenine Pathway ◽  
Xanthurenic Acid ◽  
Control Subjects ◽  
Healthy Control

Abstract Background Altered glutamatergic neurotransmission and neuropeptide levels play a central role in migraine pathomechanism. Previously, we confirmed that kynurenic acid, an endogenous glutamatergic antagonist, was able to decrease the expression of pituitary adenylate cyclase-activating polypeptide 1–38, a neuropeptide with known migraine-inducing properties. Hence, our aim was to reveal the role of the peripheral kynurenine pathway (KP) in episodic migraineurs. We focused on the complete tryptophan (Trp) catabolism, which comprises the serotonin and melatonin routes in addition to kynurenine metabolites. We investigated the relationship between metabolic alterations and clinical characteristics of migraine patients. Methods Female migraine patients aged between 25 and 50 years (n = 50) and healthy control subjects (n = 34) participated in this study. Blood samples were collected from the cubital veins of subjects (during both the interictal/ictal periods in migraineurs, n = 47/12, respectively). 12 metabolites of Trp pathway were determined by neurochemical measurements (UHPLC-MS/MS). Results Plasma concentrations of the most Trp metabolites were remarkably decreased in the interictal period of migraineurs compared to healthy control subjects, especially in the migraine without aura (MWoA) subgroup: Trp (p < 0.025), L-kynurenine (p < 0.001), kynurenic acid (p < 0.016), anthranilic acid (p < 0.007), picolinic acid (p < 0.03), 5-hydroxy-indoleaceticacid (p < 0.025) and melatonin (p < 0.023). Several metabolites showed a tendency to elevate during the ictal phase, but this was significant only in the cases of anthranilic acid, 5-hydroxy-indoleaceticacid and melatonin in MWoA patients. In the same subgroup, higher interictal kynurenic acid levels were identified in patients whose headache was severe and not related to their menstruation cycle. Negative linear correlation was detected between the interictal levels of xanthurenic acid/melatonin and attack frequency. Positive associations were found between the ictal 3-hydroxykynurenine levels and the beginning of attacks, just as between ictal picolinic acid levels and last attack before ictal sampling. Conclusions Our results suggest that there is a widespread metabolic imbalance in migraineurs, which manifests in a completely depressed peripheral Trp catabolism during the interictal period. It might act as trigger for the migraine attack, contributing to glutamate excess induced neurotoxicity and generalised hyperexcitability. This data can draw attention to the clinical relevance of KP in migraine.

scholarly journals A bottom up approach towards artificial oxygenases by combining iron coordination complexes and peptides

2017 ◽  
Vol 8 (5) ◽  
pp. 3660-3667 ◽  
Author(s):  
Olaf Cussó ◽  
Michael W. Giuliano ◽  
Xavi Ribas ◽  
Scott J. Miller ◽  
Miquel Costas
Keyword(s):  
Hydrogen Peroxide ◽  
Coordination Complexes ◽  
Asymmetric Epoxidation ◽  
Coordination Complex ◽  
High Yield ◽  
Aqueous Hydrogen Peroxide ◽  
Bottom Up ◽  
Iron Coordination

The combination of peptides and a chiral iron coordination complex catalyzes high yield highly asymmetric epoxidation with aqueous hydrogen peroxide.

Synthesis, characterization, and in vitro evaluation of new coordination complexes of platinum(ii) and rhenium(i) with a ligand targeting the translocator protein (TSPO)

2014 ◽  
Vol 43 (43) ◽  
pp. 16252-16264 ◽  
Author(s):  
Nicola Margiotta ◽  
Nunzio Denora ◽  
Sara Piccinonna ◽  
Valentino Laquintana ◽  
Francesco Massimo Lasorsa ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Coordination Complexes ◽  
Translocator Protein ◽  
Microglial Cells ◽  
In Vitro Evaluation

The 18 kDa translocator protein (TSPO) is overexpressed in many cancers and is also abundant in activated microglial cells occurring in neurodegenerative diseases.

scholarly journals Redox Properties of 8-Quinolinol and Implications for its Mode of Action

2011 ◽  
Vol 6 (5) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Vladimir Chobot ◽  
Sigrid Drage ◽  
Franz Hadacek
Keyword(s):  
Antioxidant Activity ◽  
Cyclic Voltammetry ◽  
Complex Formation ◽  
Mode Of Action ◽  
Reactive Oxygen Species Generation ◽  
Reducing Power ◽  
Free Form ◽  
Cytotoxic Activities ◽  
Major Mode ◽  
Deoxyribose Degradation

8-Quinolinol (oxine, 8-hydroxyquinoline) is a simple aromatic alkaloid with allelopathic, antibacterial, antifungal, and cytotoxic activities. Generally, it is assumed that 8-quinolinol toxicity depends on transition metal chelation that negatively affects their availability for metalloenzymes in the cell or reactive oxygen species generation (ROS), which are formed following reduction of molecular oxygen by autoxidation of the redox active metal central atom of the 8-quinolinol complex. On the contrary, beneficial effects of 8-quinolinol and its derivatives in the medication of certain degenerative diseases are known. In this context, the activity of 8-quinolinol derivatives is attributed to their antioxidant activity following iron complex formation. To address this controversial issue, we explore the possible anti- or pro-oxidant effects of 8-quinolinol and its iron complexes in the deoxyribose degradation assay, by cyclic voltammetry and in a biological assay. The antibacterial effects of 8-quinolinol and its complex with iron were evaluated on Curtobacterium flaccumfacies and Paenibacillus amylolyticus. 8-Quinolinol showed strong antioxidant activity in the deoxyribose degradation assay. This activity may not depend exclusively on iron chelation, but probably more on the notable reducing properties of 8-quinolinol; it proved to be a more efficient antioxidant than the flavonoids catechin and quercetin. By contrast, 8-quinolinol showed no pro-oxidative effects in the deoxyribose degradation assay, both in free form and in complex with iron, as it may occur with redox cyclers. Cyclic voltammetry confirmed this too. 8-Quinolinol significantly inhibited bacterial growth and respiration. Idiosyncratically, its 50:1 mixture with iron(III) ions was less active compared with free 8-quinolinol; it even caused a U-shaped nonlinear hormetic effect on growth and failed to inhibit respiration as totally as the pure mixture; the respiration was even accelerated compared with the control as a result of lower stress. Our results support the notion that complex formation with either iron or other transition metals affects the reducing power of 8-quinolinol, but, in contrast to general assumptions, this study finds no support that complex formation with iron represents the major mode of action.

scholarly journals Modulation of Hippocampal Synaptic Transmission by the Kynurenine Pathway Member Xanthurenic Acid and Other VGLUT Inhibitors

2013 ◽  
Vol 38 (6) ◽  
pp. 1060-1067 ◽  
Author(s):  
S A Neale ◽  
C S Copeland ◽  
V N Uebele ◽  
F J Thomson ◽  
T E Salt
Keyword(s):  
Synaptic Transmission ◽  
Kynurenine Pathway ◽  
Xanthurenic Acid

scholarly journals Identification and Comparative Study of Invitro Antioxidant Potential of Fractionated Hydroalcoholic Extract of Phyllanthus Niruri Linn

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Gayathri Rajamanickam ◽  
Manju S. L.
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Neurodegenerative Diseases ◽  
High Performance ◽  
Defense Mechanism ◽  
Antioxidant Activities ◽  
Natural Antioxidant ◽  
Total Phenolic ◽  
Activity Measurement ◽  
Phyllanthus Niruri

It is apparent that varieties of plants have the potential to show numerous preventive and therapeutic activities that may be relevant to the treatment of disorders caused by oxidative stress and free radicals. A variety of herbal extracts and their phyto components have been demonstrated to exert antioxidant activities, either by directly stimulating antioxidant response genes or by potentiating the bodies` own natural antioxidant defense mechanism. This study reported the high-performance liquid chromatography, invitro antioxidant activity, measurement of total phenolic and flavonoid contents of various solvent extracts of whole plant of Phyllanthus niruri in order to find possible treatment of disorders caused by oxidative stress such as neurodegenerative diseases. Results obtained revealed that, ethyl acetate fractions of P. niruri whole plants possess high flavonoid and polyphenolic compounds which ultimately leads to the potent antioxidant activity than other polar and nonpolar solvent fractions. Thus, this study suggests that, these fractions can be used as a potent source of natural antioxidant there by it can be used for the further investigation for the treatment of neurodegenerative diseases and other free radical induced pathological conditions.

Association of markers of inflammation, the kynurenine pathway and B vitamins with age and mortality, and a signature of inflammaging

2021 ◽  
Author(s):  
Pierre-Antoine Dugué ◽  
Allison M Hodge ◽  
Arve Ulvik ◽  
Per M Ueland ◽  
Øivind Midttun ◽  
...  
Keyword(s):  
Cox Regression ◽  
Kynurenine Pathway ◽  
Health Study ◽  
Xanthurenic Acid ◽  
Markers Of Inflammation ◽  
Par Index ◽  
Vitamin Status ◽  
Melbourne Collaborative Cohort Study ◽  
Index Ratio ◽  
B Vitamin

Abstract Background Inflammation is a key feature of aging. We aimed to i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality, ii) develop a signature of ‘inflammaging’. Methods Thirty-four blood markers relating to inflammation, B vitamin status and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age=59 years) and follow-up (median age=70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with two marker scores calculated across all markers associated with age and mortality, respectively. Results The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, IL-6, TNF-α, several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5´-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, CRP, quinolinic acid, PAr index, and KTR. The inflammaging signature included ten markers and was strongly associated of mortality (HR per SD=1.40, 95%CI:1.24-1.57, P=2x10 -8), similar to scores based on all age-associated (HR=1.38, 95%CI:1.23-1.55, P=4x10 -8) and mortality-associated markers (HR=1.43, 95%CI:1.28-1.60, P=1x10 -10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study. Conclusion Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on ten markers was strongly associated with mortality.

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