Effects of Fenofibrate and Gemfibrozil on Kynurenic Acid Production in Rat Kidneys In Vitro: Old Drugs, New Properties.

Autor: Zakrocka I; Department of Nephrology, Medical University, Jaczewskiego Street 8, 20-954 Lublin, Poland., Kocki T; Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego Street 8b, 20-090 Lublin, Poland., Urbańska E; Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego Street 8b, 20-090 Lublin, Poland., Załuska W; Department of Nephrology, Medical University, Jaczewskiego Street 8, 20-954 Lublin, Poland.
Jazyk: angličtina
Zdroj: Life (Basel, Switzerland) [Life (Basel)] 2023 Nov 02; Vol. 13 (11). Date of Electronic Publication: 2023 Nov 02.
DOI: 10.3390/life13112154
Abstrakt: Kidney dysfunction significantly increases the cardiovascular risk, even in cases of minor functional declines. Hypertriglyceridemia is the most common lipid abnormality reported in patients with kidney disorders. PPAR-α (peroxisome proliferator-activated receptor-α) agonists called fibrates are the main agents used to lower triglyceride levels. Kynurenic acid (KYNA) is a tryptophan (Trp) derivative directly formed from L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). KYNA is classified as a uremic toxin, the level of which is correlated with kidney function impairments and lipid abnormalities. The aim of this study was to analyze the effect of the most commonly used triglyceride-lowering drugs, fenofibrate and gemfibrozil, on KYNA production and KAT activity in rat kidneys in vitro. The influence of fenofibrate and gemfibrozil on KYNA formation and KAT activity was tested in rat kidney homogenates in vitro. Fenofibrate and gemfibrozil at 100 µM-1 mM significantly inhibited KYNA synthesis in rat kidney homogenates. Both fibrates directly affected the KAT I and KAT II isoenzyme activities in a dose-dependent manner at similar concentrations. The presented results reveal the novel mechanism of action of fibrates in the kidneys and suggest their potential role in kidney function protection beyond the well-known anti-hyperlipidemic effect.
Databáze: MEDLINE
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