Targeting of the kynurenic acid across the blood–brain barrier by core-shell nanoparticles

Varga, Noémi; Csapó, Edit; Majláth, Zsófia; Ilisz, István; Krizbai, István A.; Wilhelm, Imola; Knapp, Levente; Toldi, József; Vécsei, László; Dékány, Imre

doi:10.1016/j.ejps.2016.02.012

Cited by 43 publications

(31 citation statements)

References 42 publications

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“…Naturally, the thermodynamic state functions are standard values as presented in Table 1. (corrections: page 1, abstract; page 3, line 1; page 8, line 27; page 10, line 18,23,25,26). However, the K A is also standard value, but according to IUPAC nomenclature both the K A and the K A° are also suitable.…”

Section: " the Equations (8) And (9) Are Basic Thermodynamic Equationmentioning

confidence: 99%

Thermodynamic and kinetic characterization of pH-dependent interactions between bovine serum albumin and ibuprofen in 2D and 3D systems

Csapó

Juhász

Varga

et al. 2016

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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Section: " the Equations (8) And (9) Are Basic Thermodynamic Equationmentioning

confidence: 99%

Thermodynamic and kinetic characterization of pH-dependent interactions between bovine serum albumin and ibuprofen in 2D and 3D systems

Csapó

Juhász

Varga

et al. 2016

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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“…42 An increase in KYNA concentration in peripheral tissues does not lead to elevation of its concentrations in the CNS, due to inadequate penetration through the bloodbrain barrier. 43 Thus, it is possible that KYNA is related to renovascular hypertension in the periphery, but its central effect on blood vessel wall may be distinct. On the other hand, KYNA can act by different receptors; for example, it is an endogenous ligand for AhR, 44 whose activation by industrial dioxins can impair endothelium-dependent vasodilatation leading to hypertension.…”

Section: Discussionmentioning

confidence: 99%

The activation of the kynurenine pathway in a rat model with renovascular hypertension

Bartosiewicz

Kamiński

Pawlak

et al. 2017

Exp Biol Med (Maywood)

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Hypertension is a serious condition that can lead to many health problems. The mechanisms underlying this process are still not fully understood. The kynurenine pathway may be involved in the occurrence and progression of hypertension. The purpose of this study was to examine the activity of peripheral kynurenine pathway in rats with renovascular hypertension in Goldblatt 2K1C model. Hypertension was induced in the experimental groups by constricting the renal artery of the left kidney of the rats. Determination of tryptophan (Trp) and kynurenine pathway metabolites was assessed by high-performance liquid chromatography in plasma and tissues obtained at 4, 8, and 16 weeks after the surgical intervention or sham surgery. Levels of Ang II were evaluated using commercial immuno-enzymatic ELISA kits. Surgical treatment led to increased values of mean blood pressure and systolic blood pressure, whereas Trp concentrations were decreased in experimental animals compared to appropriate controls. Simultaneously, the considerable increment of kynurenine pathway components and a significant increase in the activity of tryptophan 2,3-dioxygenase were observed in rats with developed hypertension in comparison with controls. There were no differences between Ang II levels in controls and experimental groups. The inverse relationship was between plasma Trp and both SBP and Ang II values, and Trp independently affected Ang II concentrations in hypertensive rats. In contrast, tryptophan 2,3-dioxygenase activity and plasma kynurenine metabolites positively correlated with blood pressure values as well as with Ang II levels in these animals. Moreover, kynurenine was independently connected with MBP. Renovascular hypertension influences kynurenine pathway and leads to an imbalance in Trp and its metabolite levels. Tryptophan 2,3-dioxygenase and part of the kynurenine metabolites in plasma and tissues positively correlated with blood pressure values and Ang II levels. Although the mechanisms underlying this phenomenon are unclear, our experiment showed a link between renovascular hypertension and activation of kynurenine pathway. Impact statement As hypertension is a major health problem, our research has focused on the connection between the kynurenine pathway and hypertension. We assessed the levels of the main metabolites of dietary tryptophan and analyzed its levels in terms of high blood pressure. The results of our work indicated that in the renovascular rat's model of hypertension, an alteration of the kynurenine pathway occurred. According to our knowledge, this is the first study that has investigated in a comprehensive manner the alteration of the kynurenine pathway under the condition of elevated blood pressure. On the one hand, the work supports a better understanding of pathophysiological basics of the occurrence of hypertension, and on the other hand it provides potential opportunities to treat this disease.

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“…Összefoglalva megállapítható [44,45], hogy a BSA/ KYNA/PAH nanokapszulából a KYNA szignifikánsan nagyobb mennyiségben jut át a vér-agy-gáton, mint a szabad KYNA. A BSA/KYNA/PAH nanokapszula alkalmas gyógyszermolekulák szállítására, leadására a véragy-gáton való átjuttatás révén a központi idegrendszerben.…”

Section: Szabályozott Hatóanyag-leadású Rendszerekunclassified

Kinureninek és gyógyszerkutatás

Tóth

Fülöp

Szatmári

et al. 2020

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Absztrakt: A kinureninek manapság intenzív érdeklődés tárgyát képezik, mivel számos fiziológiás és patológiás folyamatban részt vesznek. Az esszenciális aminosav triptofán elsősorban a kinurenin-útvonalon keresztül metabolizálódik. A lebomlás során kinurenin-aminotranszferázok segítségével keletkezik az egyik fontos termék, a kinurénsav. A kinurénsav excitatorikus receptorok ligandja, neuroprotektív tulajdonságú. A kinurénsav szintjének abnormális csökkenése vagy növekedése a neurotranszmitter-rendszerek egyensúlyának felborulásához vezethet, és ez számos neurodegeneratív és neuropszichiátriai betegségben megfigyelhető. A kinurénsav a poláros szerkezete miatt nehezen jut át a vér–agy-gáton, emiatt közvetlenül nem alkalmas terápiás célokra. Ezért kutatásunk célja olyan kinurénsav-analógok előállítása és farmakológiai tesztelése volt, melyek a vér–agy-gáton könnyebben átjutnak. Az újonnan szintetizált kinurénsav-analógok hatékonynak bizonyultak több idegrendszeri betegség (migrén, Huntington-kór) modelljében. A kinurénsav-származékokkal kapott eredmények szerint e vegyületek új terápiás célpontot jelenthetnek a neurodegeneratív betegségek kezelésében. Kutatási eredményeink alapján számos szabadalmi bejelentést benyújtottunk. Orv Hetil. 2020; 161(12): 443–451.

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Targeting of the kynurenic acid across the blood–brain barrier by core-shell nanoparticles

Cited by 43 publications

References 42 publications

Thermodynamic and kinetic characterization of pH-dependent interactions between bovine serum albumin and ibuprofen in 2D and 3D systems

Thermodynamic and kinetic characterization of pH-dependent interactions between bovine serum albumin and ibuprofen in 2D and 3D systems

The activation of the kynurenine pathway in a rat model with renovascular hypertension

Kinureninek és gyógyszerkutatás

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