Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel

Yue, Ma; Ran, Fenglin; Xin, Mingyan; Gou, Xueyan; Wang, Xinyi; Wu, Xinan

doi:10.1016/j.jpha.2023.05.007

Journal of Pharmaceutical Analysis

2023

DOI: 10.1016/j.jpha.2023.05.007

|View full text |Cite

Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel

Ma Yue

Fenglin Ran

Mingyan Xin

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2023

2024

Publication Types

Select...

Article4

Relationship

Self Cite0

Independent4

Authors

Journals

Cited by 4 publications

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

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

Zakrocka,

Targowska-Duda,

Kocki

et al. 2024

Pharmacol. Rep

View full text Add to dashboard Cite

Background Loop 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. Methods Quantitative 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. Results All 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. Conclusions Our 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. Graphical abstract

show abstract

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

Zakrocka,

Targowska-Duda,

Kocki

et al. 2024

Pharmacol. Rep

View full text Add to dashboard Cite

show abstract

Effect of probenecid on blood levels and renal elimination of furosemide and endogenous compounds in rats: Discovery of putative organic anion transporter biomarkers

Thakur,

Saradhi Mettu,

Singh

et al. 2023

Biochemical Pharmacology

View full text Add to dashboard Cite

The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy

Stone,

Darlington,

Badawy

et al. 2024

IJMS

View full text Add to dashboard Cite

It has been unequivocally established that kynurenic acid has a number of actions in a variety of cells and tissues, raising, in principle, the possibility of targeting its generation, metabolism or sites of action to manipulate those effects to a beneficial therapeutic end. However, many basic aspects of the biology of kynurenic acid remain unclear, potentially leading to some confusion and misinterpretations of data. They include questions of the source, generation, targets, enzyme expression, endogenous concentrations and sites of action. This essay is intended to raise and discuss many of these aspects as a source of reference for more balanced discussion. Those issues are followed by examples of situations in which modulating and correcting kynurenic acid production or activity could bring significant therapeutic benefit, including neurological and psychiatric conditions, inflammatory diseases and cell protection. More information is required to obtain a clear overall view of the pharmacological environment relevant to kynurenic acid, especially with respect to the active concentrations of kynurenine metabolites in vivo and changed levels in disease. The data and ideas presented here should permit a greater confidence in appreciating the sites of action and interaction of kynurenic acid under different local conditions and pathologies, enhancing our understanding of kynurenic acid itself and the many clinical conditions in which manipulating its pharmacology could be of clinical value.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel

Cited by 4 publications

References 53 publications

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

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

Effect of probenecid on blood levels and renal elimination of furosemide and endogenous compounds in rats: Discovery of putative organic anion transporter biomarkers

The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy

Contact Info

Product

Resources

About