Evidence mapPaperPMID 39261392Full record

ArticlePharmacological reports : PR2024

Loop diuretics inhibit kynurenic acid production and kynurenine aminotransferases activity in rat kidneys.

Izabela Zakrocka, Katarzyna M Targowska-Duda, Tomasz Kocki, Waldemar Turski, Ewa M Urbańska, Wojciech Załuska

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Article in Pharmacological reports : PR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Izabela ZakrockaDepartment of Nephrology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland. izabela.zakrocka@umlub.pl.ORCID http://orcid.org/0000-0001-5251-7763
Katarzyna M Targowska-DudaDepartment of Biopharmacy, Medical University of Lublin, Chodźki 4a, 20-093, Lublin, Poland.
Tomasz KockiDepartment of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland.
Waldemar TurskiDepartment of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland.
Ewa M UrbańskaDepartment of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b, 20-090, Lublin, Poland.
Wojciech ZałuskaDepartment of Nephrology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland.

Funding

Ministerstwo Edukacji i Nauki MNmb 515/2016Uniwersytet Medyczny w Lublinie 384
6 · The paper itself

Abstract

backgroundLoop diuretics became a cornerstone in the therapy of hypervolemia in patients with chronic kidney disease or heart failure. Apart from the influence on water and electrolyte balance, these drugs were shown to inhibit tissue fibrosis and renin-angiotensin-system activity. The kynurenine (KYN) pathway products are suggested to be uremic toxins. Kynurenic acid (KYNA) is synthesized by kynurenine aminotransferases (KATs) in the brain and periphery. The cardiovascular and renal effects of KYNA are well documented. However, high KYNA levels have been correlated with the rate of kidney damage and its complications. Our study aimed to assess the effect of loop diuretics, ethacrynic acid, furosemide, and torasemide on KYNA synthesis and KATs activity in rat kidneys in vitro.

methodsQuantitative analyses of KYNA were performed using fluorimetric HPLC detection. Additionally, molecular docking studies determined the possible interactions of investigated compounds with an active site of KAT I and KAT II.

resultsAll studied drugs inhibited KYNA production in rat kidneys in vitro at 0.5-1.0 mmol/l concentrations. Only ethacrynic acid at 1.0 mmol/l concentration significantly lowered KAT I and KAT II activity in kidney homogenates, whereas other drugs were ineffective. Molecular docking results indicated the common binding site for each of the studied loop diuretics and KYNA. They suggested possible residues involved in their binding to the active site of both KAT I and KAT II model.

conclusionsOur study reveals that loop diuretics may decrease KYNA synthesis in rat kidneys in vitro. The presented results warrant further research in the context of KYN pathway activity regulation by loop diuretics.

Indexed as

KidneyKynurenic AcidMolecular Docking SimulationSodium Potassium Chloride Symporter InhibitorsTransaminasesAnimalsEthacrynic AcidFurosemideMaleRatsRats, WistarTorsemideEthacrynic AcidFurosemideKynurenic Acidkynurenine-oxoglutarate transaminaseSodium Potassium Chloride Symporter InhibitorsTorsemideTransaminasesKidneyKynurenic acidKynurenineKynurenine pathwayLoop diureticsTryptophan

Identifiers

PMID39261392
PMCPMC11582277

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.