Liver and Kidney Kynurenine Aminotransferase Activity in Different Strains of Rats

Costa, Carlo Virgilio Luigi; Ragazzi, Eugenio; Caparrotta, Laura; Bertazzo, Antonella; Biasiolo, M.; Allegri, Graziella

doi:10.1007/978-1-4615-4709-9_80

Cited by 5 publications

(2 citation statements)

References 39 publications

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“…Gene expression profiling conducted on publically available microarray data revealed that KAT isoforms are expressed at considerable level in both rat and human kidneys. This data stands in line with previously published results on positive activity of KATs in renal tissue (Costa et al 1999). Further data mining revealed only a single, negative experimental result regarding effects of ARBs on the expression of KAT-coding genes in kidney.…”

Section: Discussionsupporting

confidence: 91%

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

Zakrocka

Targowska-Duda

Wnorowski

et al. 2018

Naunyn-Schmiedeberg's Arch Pharmacol

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Glutamate (GLU) mainly through N-methyl-D-aspartate (NMDA) receptors plays pivotal role in kidney function regulation. Kynurenic acid (KYNA), a GLU receptors antagonist, is synthesized from kynurenine by kynurenine aminotransferases (KATs). Previously, it was shown that angiotensin II type 1 receptor blockers (ARBs) decrease KYNA production in rat brain in vitro. The aim of this study was to examine the influence of six ARBs: candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan on KYNA production on rat kidney in vitro. The effect of ARBs was determined in kidney homogenates and on isolated KAT II enzyme. Among tested ARBs, irbesartan was the most effective KYNA synthesis inhibitor with IC 50 of 14.4 μM. Similar effects were observed after losartan (IC 50 45.9 μM) and olmesartan administration (IC 50 108.1 μM), whereas candesartan (IC 50 475.3 μM), valsartan (IC 50 513.9 μM), and telmisartan (IC 50 669.5 μM) displayed lower activity in KYNA synthesis inhibition in rat kidney homogenates in vitro. On the other hand, valsartan (IC 50 27.5 μM) was identified to be the strongest KAT II inhibitor in rat kidney in vitro. Candesartan, losartan, and telmisartan suppressed KAT II activity with IC 50 equal to 83.2, 83.3, and 108.3 μM, respectively. Olmesartan and irbesartan were the weakest KAT II inhibitors with IC 50 values of 237.4 and 809.9 μM, respectively. Moreover, molecular docking suggested that studied ARBs directly bind to an active site of KAT II. In conclusion, our results indicate that ARBs decrease KYNA synthesis in rat kidney through enzymatic inhibition of KAT II, which may have impact on kidney function.

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Section: Discussionsupporting

confidence: 91%

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

Zakrocka

Targowska-Duda

Wnorowski

et al. 2018

Naunyn-Schmiedeberg's Arch Pharmacol

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show abstract

“…In the human body, KYNA is produced by kynurenine aminotransferase isomers 1-4, which are present in the colonic epithelium, liver, kidney, muscle, and omental fat. [40][41][42] If the systemic inflammatory state in UC could induce production from these other tissues, it may lead to KYNA production out of proportion to intestinal activation of the pathway. Alternatively, there are environmental sources of KYNA in common foods such as potatoes, honey, and broccoli, which are rich sources of KYNA in the diet.…”

Section: Discussionmentioning

confidence: 99%