Suppr超能文献

非诺贝特和吉非贝齐对大鼠肾脏体外犬尿氨酸生成的影响:老药新特性

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

作者信息

Zakrocka Izabela, Kocki Tomasz, Urbańska Ewa, Załuska Wojciech

机构信息

Department of Nephrology, Medical University, Jaczewskiego Street 8, 20-954 Lublin, Poland.

Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego Street 8b, 20-090 Lublin, Poland.

出版信息

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

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.

摘要

肾功能不全显著增加心血管风险,即使在功能轻微下降的情况下也是如此。高甘油三酯血症是肾脏疾病患者中最常见的脂质异常。称为贝特类药物的过氧化物酶体增殖物激活受体-α(PPAR-α)激动剂是用于降低甘油三酯水平的主要药物。犬尿喹啉酸(KYNA)是一种色氨酸(Trp)衍生物,由犬尿氨酸转氨酶(KATs)直接从L-犬尿氨酸(L-KYN)形成。KYNA被归类为一种尿毒症毒素,其水平与肾功能损害和脂质异常相关。本研究的目的是分析最常用的降甘油三酯药物非诺贝特和吉非贝齐对大鼠肾脏体外犬尿喹啉酸产生和犬尿氨酸转氨酶活性的影响。在大鼠肾脏匀浆中体外测试非诺贝特和吉非贝齐对犬尿喹啉酸形成和犬尿氨酸转氨酶活性的影响。100 µM-1 mM的非诺贝特和吉非贝齐显著抑制大鼠肾脏匀浆中犬尿喹啉酸的合成。两种贝特类药物在相似浓度下均以剂量依赖性方式直接影响犬尿氨酸转氨酶I和犬尿氨酸转氨酶II同工酶活性。所呈现的结果揭示了贝特类药物在肾脏中的新作用机制,并表明它们在肾脏功能保护中的潜在作用,这超出了众所周知的抗高脂血症作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5359/10672417/e5f545c2daa4/life-13-02154-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验