Abstract: FR-PO238
Effect of Ibuprofen on Kynurenic Acid Production and Kynurenine Aminotransferases Activity in Rat Kidneys
Session Information
- Pharmacology
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)
- 1900 Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)
Authors
- Zakrocka, Izabela, Uniwersytet Medyczny w Lublinie, Lublin, Lubelskie, Poland
- Zaluska, Wojciech T., Uniwersytet Medyczny w Lublinie, Lublin, Lubelskie, Poland
Background
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics and anti-inflammatory agents. Inhibition of cyclooxygenase, leading to decreased prostaglandin synthesis, is their main mechanism of action, also responsible for NSAIDs renal side effects. Ibuprofen, one of the most popular NSAID, is known to cause acute kidney injury, thus increasing the risk of chronic kidney disease.
The metabolite of tryptophan, kynurenic acid (KYNA), is made from L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). KAT I and KAT II are the best studied KAT isoenzymes. KYNA is a non-selective antagonist of ionotropic glutamatergic receptors. Natriuretic, anti-inflammatory, chronotropic negative and hypotensive properties of KYNA were previously described.
The goal of the present study was to examine the effect of ibuprofen, commonly used over-the-counter NSAID, on KYNA production and the activity of KAT I and KAT II, in rat kidney in vitro.
Methods
The effect of ibuprofen on KYNA production together with KAT I and KAT II activity was examined in rat kidney homogenates in vitro after 2 hours incubation in the presence of L-KYN and ibuprofen. The drug was tested at the concentration of 1 µM, 10 µM, 50 µM, 100 µM, 500 µM and 1 mM. KYNA formation during enzymatic reaction was measured with the use of high performance liquid chromatography (HPLC) with fluorometric detector. All applicable international, national and institutional guidelines for the care and use of animals were followed. All procedures performed in this study involving animals were in accordance with the ethical standards of the Local Ethics Committee for Animal Experiments.
Results
Ibuprofen at 500 µM and 1 mM decreased KYNA production in kidney homogenates in vitro to 78% (P < 0.05) and 46% (P < 0.001) of control value, respectively. At 1 mM concentration ibuprofen lowered renal KAT I activity in vitro to 82% (P < 0.05) of control value. Additionally, ibuprofen at 500 µM and 1 mM concentration decreased kidney KAT II activity in vitro to 68% (P < 0.05) and 43% (P < 0.05) of control value, respectively.
Conclusion
Ibuprofen decreases KYNA synthesis in rat kidney in vitro by inhibiting KAT I and KAT II isoenzymes. Results of our study indicate a novel mechanism of ibuprofen’s action in the kidney. Its possible relationship with NSAIDs-induced nephrotoxicity needs further clarifications.