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. 2023 Nov 2;13(11):2154.
doi: 10.3390/life13112154.

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

Izabela Zakrocka  1 , Tomasz Kocki  2 , Ewa Urbańska  2 , Wojciech Załuska  1
Affiliations

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

Izabela Zakrocka et al. Life (Basel). .

Abstract

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.

Keywords: fenofibrate; gemfibrozil; hypertriglyceridemia; kidney; kynurenic acid.

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Conflict of interest statement

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Effect of fibrates on KYNA production in rat kidneys in vitro. Data are shown as percentage of KYNA synthesis, means ± SD, n = 6, and are plotted against drug concentration on a logarithmic scale. ANOVA followed by Tukey’s multiple comparison test. The figure was prepared in GraphPad Prism 6. * p < 0.05, *** p < 0.001.
Figure 2
Figure 2
Effect of fibrates on KAT I activity in rat kidneys in vitro. Data presenting the enzymatic activity as percentage of KYNA synthesis, mean ± SD, n = 3, are plotted against drug concentration on a logarithmic scale. ANOVA followed by Tukey’s multiple comparison test. The figure was prepared in GraphPad Prism 6. * p < 0.05, ** p < 0.01.
Figure 3
Figure 3
Effect of fibrates on KAT II activity in rat kidneys in vitro. Data presenting the enzymatic activity as percentage of KYNA synthesis, mean ± SD, n = 3, are plotted against drug concentration on a logarithmic scale. ANOVA followed by Tukey’s multiple comparison test. The figure was prepared in GraphPad Prism 6. * p < 0.05, ** p < 0.01, *** p < 0.001.
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