Angiotensin II type 1 receptor blockers decrease kynurenic acid production in rat kidney in vitro

Zakrocka, Izabela; Targowska-Duda, Katarzyna M.; Wnorowski, Artur; Kocki, Tomasz; Jóźwiak, Krzysztof; Turski, Waldemar A.

doi:10.1007/s00210-018-1572-7

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…Similarly, angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers (ARBs) were observed to modify kidney KYNA levels. ACE-I lowers the KYNA concentration in rat kidney homogenates in vitro without affecting KAT activity [118], and ARBs decrease KYNA production by KAT inhibition in rat kidneys in vitro [119,120]. Unfortunately, although Chmiel-Perzyńska et al showed that after 4 weeks of administration, losartan decreases brain KYNA concentration in a rat model of diabetes mellitus, data on the long-term effect of ARBs on kidney KYN pathway activity are lacking [121].…”

Section: Drugs Affecting Kynurenine Pathway In the Kidneymentioning

confidence: 99%

Kynurenine pathway in kidney diseases

Zakrocka

Załuska

2021

Pharmacol. Rep

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Kidney diseases have become one of the most common health care problems. Due to a growing number of advanced aged patients with concomitant disorders the prevalence of these diseases will increase over the coming decades. Despite available laboratory tests, accurate and rapid diagnosis of renal dysfunction has yet to be realized, and prognosis is uncertain. Moreover, data on diagnostic and prognostic markers in kidney diseases are lacking. The kynurenine (KYN) pathway is one of the routes of tryptophan (Trp) degradation, with biologically active substances presenting ambiguous properties. The KYN pathway is known to be highly dependent on immunological system activity. As the kidneys are one of the main organs involved in the formation, degradation and excretion of Trp end products, pathologies involving the kidneys result in KYN pathway activity disturbances. This review aims to summarize changes in the KYN pathway observed in the most common kidney disease, chronic kidney disease (CKD), with a special focus on diabetic kidney disease, acute kidney injury (AKI), glomerulonephritis and kidney graft function monitoring. Additionally, the importance of KYN pathway activity in kidney cancer pathogenesis is discussed, as are available pharmacological agents affecting KYN pathway activity in the kidney. Despite limited clinical data, the KYN pathway appears to be a promising target in the diagnosis and prognosis of kidney diseases. Modulation of KYN pathway activity by pharmacological agents should be considered in the treatment of kidney diseases.

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Section: Drugs Affecting Kynurenine Pathway In the Kidneymentioning

confidence: 99%

Kynurenine pathway in kidney diseases

Zakrocka

Załuska

2021

Pharmacol. Rep

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“…The results indicate that NMDAR modulators with tonic vasodilatatory effect on the glomerular microvasculature might be used as a useful therapeutic tool to regulate TGF and glomerular filtration. Another piece of evidence regarding the function of NMDAR the kidney is the paper of Zakrocka et al [ 85 ], where authors demonstrated that angiotensin II type 1 receptor blockers decreased production of KYNA in a dose-dependent manner via enzymatic inhibition of KYNA synthesis, which influenced kidney function [ 85 ].…”

Section: Distinctive Physiological and Pathophysiological Roles Ofmentioning

confidence: 99%

Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney

et al. 2020

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N-Methyl-d-aspartate receptor (NMDAR) is a glutamate-gated ionotropic receptor that intervenes in most of the excitatory synaptic transmission within the central nervous system (CNS). Aside from being broadly distributed in the CNS and having indispensable functions in the brain, NMDAR has predominant roles in many physiological and pathological processes in a wide range of non-neuronal cells and tissues. The present review outlines current knowledge and understanding of the physiological and pathophysiological functions of NMDAR in the kidney, an essential excretory and endocrine organ responsible for the whole-body homeostasis. The review also explores the recent findings regarding signaling pathways involved in NMDAR-mediated responses in the kidney. As established from diverse lines of research reviewed here, basal levels of receptor activation within the kidney are essential for the maintenance of healthy tubular and glomerular function, while a disproportionate activation can lead to a disruption of NMDAR’s downstream signaling pathways and a myriad of pathophysiological consequences.

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“…In the context of the available literature, the observed decrease in kidney KYNA production may rather serve as a prognostic marker of fibrate effectiveness. Renin-angiotensin system inhibitors reduce kidney KYNA synthesis [53,54]. Furthermore, lowered serum levels of the KYNA precursor KYN in diabetic CKD patients receiving renin-angiotensin system inhibitors, compared to nonusers, were demonstrated [55].…”

Section: Discussionmentioning

confidence: 99%

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

Zakrocka,

Kocki,

Urbańska

et al. 2023

Life

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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.

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Angiotensin II type 1 receptor blockers decrease kynurenic acid production in rat kidney in vitro

Cited by 8 publications

References 30 publications

Kynurenine pathway in kidney diseases

Kynurenine pathway in kidney diseases

Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney

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

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