The protective effect of 1-methyltryptophan isomers in renal ischemia-reperfusion injury is not exclusively dependent on indolamine 2,3-dioxygenase inhibition. Čepcová D, Kema IP, Sandovici M, Deelman LE, Šišková K, Klimas J, Vavrinec P, Vavrincová-Yaghi D. Biomed Pharmacother. 2021 Mar;135:111180. doi: 10.1016/j.biopha.2020.111180.

A case of severe chlorite poisoning successfully treated with early administration of methylene blue, renal replacement therapy, and red blood cell transfusion: case report. Gebhardtova A, Vavrinec P, Vavrincova-Yaghi D, Seelen M, Dobisova A, Flassikova Z, Cikova A, Henning RH, Yaghi A. Medicine (Baltimore). 2014 Aug;93(9):e60. doi: 10.1097/MD.0000000000000060

Local gene therapy with indoleamine 2,3-dioxygenase protects against development of transplant vasculopathy in chronic kidney transplant dysfunction. Vavrincova-Yaghi D, Deelman LE, van Goor H, Seelen MA, Vavrinec P, Kema IP, Gomolcak P, Benigni A, Henning RH, Sandovici M. Gene Ther. 2016 Nov;23(11):797-806. doi: 10.1038/gt.2016.59.

Early Posttransplant Tryptophan Metabolism Predicts Long-term Outcome of Human Kidney Transplantation. Vavrincova-Yaghi D, Seelen MA, Kema IP, Deelman LE, van der Heuvel MC, Breukelman H, Van den Eynde BJ, Henning RH, van Goor H, Sandovici M. Transplantation. 2015 Aug;99(8):e97-104. doi: 10.1097/TP.0000000000000603. 

Gene therapy with adenovirus-delivered indoleamine 2,3-dioxygenase improves renal function and morphology following allogeneic kidney transplantation in rat. Vavrincova-Yaghi D, Deelman LE, Goor H, Seelen M, Kema IP, Smit-van Oosten A, Zeeuw D, Henning RH, Sandovici M. J Gene Med. 2011 Jul;13(7-8):373-81. doi: 10.1002/jgm.1584. 

Gaál Kovalčíková A, Janovičová Ľ, Hodosy J, Bábíčková J, Vavrincová-Yaghi D, Vavrinec P, Boor P, Podracká Ľ, Šebeková K, Celec P, Tóthová Ľ. Extracellular DNA concentrations in various aetiologies of acute kidney injury. Sci Rep. 2022 Oct 7;12(1):16812. doi: 10.1038/s41598-022-21248-7. PMID: 36207374; PMCID: PMC9546839.

Kovalčíková A, Gyurászová M, Vavrincová-Yaghi D, Vavrinec P, Tóthová Ľ, Boor P, Šebeková K, Celec P. Oxidative stress in the brain caused by acute kidney injury. Metab Brain Dis. 2018 Jun;33(3):961-967. doi: 10.1007/s11011-018-0204-8. Epub 2018 Mar 7. PMID: 29516412

Renczés E, Marônek M, Gaál Kovalčíková A, Vavrincová-Yaghi D, Tóthová L, Hodosy J. Behavioral Changes During Development of Chronic Kidney Disease in Rats. Front Med (Lausanne). 2020 Jan 9;6:311. doi: 10.3389/fmed.2019.00311. PMID: 31998731; PMCID: PMC6962109.

Mišúth S, Uhrinová M, Klimas J, Vavrincová-Yaghi D, Vavrinec P. Vildagliptin improves vascular smooth muscle relaxation and decreases cellular senescence in the aorta of doxorubicin-treated rats. Vascul Pharmacol. 2021 Jun;138:106855. doi: 10.1016/j.vph.2021.106855. Epub 2021 Mar 17. PMID: 33744414.

Vavrinec P, Krivy J, Sykorova S, Bandzuchova H, Zilinska Z, Vavrincova-Yaghi D. Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients. Biomedicines. 2024 Oct 14;12(10):2338. doi: 10.3390/biomedicines12102338. PMID: 39457650; PMCID: PMC11505218.

The protective effect of 1-methyltryptophan isomers in renal ischemia-reperfusion injury is not exclusively dependent on indolamine 2,3-dioxygenase inhibition. Čepcová D, Kema IP, Sandovici M, Deelman LE, Šišková K, Klimas J, Vavrinec P, Vavrincová-Yaghi D. Biomed Pharmacother. 2021 Mar;135:111180.

Behavioral Changes During Development of Chronic Kidney Disease in Rats. Renczés E, Marônek M, Gaál Kovalčíková A, Vavrincová-Yaghi D, Tóthová L, Hodosy J. Front Med (Lausanne). 2020 Jan 9;6:311.

Vildagliptin improves vascular smooth muscle relaxation and decreases cellular senescence in the aorta of doxorubicin-treated rats. Mišúth S, Uhrinová M, Klimas J, Vavrincová-Yaghi D, Vavrinec P. Vascul Pharmacol. 2021 Jun;138:106855.

Extracellular DNA concentrations in various aetiologies of acute kidney injury. Gaál Kovalčíková A, Janovičová Ľ, Hodosy J, Bábíčková J, Vavrincová-Yaghi D, Vavrinec P, Boor P, Podracká Ľ, Šebeková K, Celec P, Tóthová Ľ. Sci Rep. 2022 Oct 7;12(1):16812. doi: 10.1038/s41598-022-21248-7. PMID: 36207374; PMCID: PMC9546839.

Enhanced Diazepam Elimination With the Molecular Adsorbents Recirculating System (MARS) in Severe Autointoxication: A Survival Case Report. Dobisova A, Vavrinec P, Vavrincova-Yaghi D, Gebhardtova A, Henning RH, Yaghi A. Case Report. Front Med (Lausanne). 2021 Mar 9;8:633250. doi: 10.3389/fmed.2021.633250. PMID: 33791324; PMCID: PMC8006414.

Cinakova A, Vavrincova-Yaghi D, Krenek P, Klimas J, Kralova E. Combination of dapagliflozin and pioglitazone lacks superiority against monotherapy in streptozotocin-induced nephropathy. Sci Rep. 2025 Jan 9;15(1):1464. doi: 10.1038/s41598-024-84487-w. PMID: 39789116; PMCID: PMC11718164.

Vavrinec P, Krivy J, Sykorova S, Bandzuchova H, Zilinska Z, Vavrincova-Yaghi D. Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients. Biomedicines. 2024 Oct 14;12(10):2338. doi: 10.3390/biomedicines12102338. PMID: 39457650; PMCID: PMC11505218.

Uremic encephalopathy. Rosner MH, Husain-Syed F, Reis T, Ronco C, Vanholder R. Kidney Int. 2022 Feb;101(2):227-241 

Acute kidney injury. John A Kellum, Paola Romagnani, Gloria Ashuntantang, Claudio Ronco , Alexander Zarbock, Hans-Joachim Anders. Nat Rev Dis Primers. 2021 Jul 15;7(1):52.

Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Platten, M., Nollen, E.A.A, Röhrig, U.F., Fallarino, F., Opitz, C.A.: Nature Reviews Drug Discovery. 2019 May;18(5):379-401.

Store–Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein Expression. Peiwen Wu, Yanxia Wang, Mark E. Davis, Jonathan E. Zuckerman, Sarika Chaudhari, Malcolm Begg, Rong Ma. J Am Soc Nephrol. 2015 Nov; 26(11): 2691–2702. 

The immunometabolic role of indoleamine 2,3-dioxygenase in atherosclerotic cardiovascular disease: immune homeostatic mechanisms in the artery wall. Daniel F J Ketelhuth. Cardiovasc Res. 2019 Jul 1;115(9):1408-1415. 

Schuermans S., Kestens C., Marques P.E.

AUTHOR FULL NAMES: Schuermans, Sara (57279202300); Kestens, Caine (59244158600); Marques, Pedro Elias (55338593700)

57279202300; 59244158600; 55338593700

Systemic mechanisms of necrotic cell debris clearance

(2024) Cell Death and Disease, 15 (8), art. no. 557, Cited 5 times.

DOI: 10.1038/s41419-024-06947-5

Imenez Silva P.H., Pepin M., Figurek A., Gutiérrez-Jiménez E., Bobot M., Iervolino A., Mattace-Raso F., Hoorn E.J., Bailey M.A., Hénaut L., Nielsen R., Frische S., Trepiccione F., Hafez G., Altunkaynak H.O., Endlich N., Unwin R., Capasso G., Pesic V., Massy Z., Wagner C.A., Andrade A., Bachmann M., Bumblyte I., Constantin Covic A., Engvig A., Fouque D., Franssen C., Gesualdo L., Goumenos D., Mani L.-Y., Marti H.-P., Mayer C., Rroji Molla M., Sakkas G., Stevens K., Vazelov E., Viggiano D., Zacharia L., Wanner C., Nitsch D., Fridolin I., Romeo M.J.S., Batinić B., Carrasco L., Gansevoort R., Martino G., Nistor I., Ortiz A., Rastenytė D., Stefan G., Tedeschi G., Bikbov B., Endlich K.H., Kurganaite J., Perico N., Remuzzi G., Blankestijn P., Eckardt K.-U., Fliser D., Konig M., Rychlik I., Deleidi M., Reusz G., Farisco M., Capolongo G.

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Animal models to study cognitive impairment of chronic kidney disease

(2024) American Journal of Physiology - Renal Physiology, 326 (6), pp. F894 - F916, Cited 1 times.

DOI: 10.1152/ajprenal.00338.2023

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85194112846&doi=10.1152%2fajprenal.00338.2023&partnerID=40&md5=c556555aec3bb647fe4a9dbe7752bc61

Viggiano D., Capasso G.

AUTHOR FULL NAMES: Viggiano, Davide (55944068400); Capasso, Giovambattista (35599101500)

55944068400; 35599101500

How much time does it take to get cognitive impairment in kidney disease?

(2022) Nephrology Dialysis Transplantation, 37 (2), pp. 203 - 204, Cited 1 times.

DOI: 10.1093/ndt/gfab220

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123877692&doi=10.1093%2fndt%2fgfab220&partnerID=40&md5=94d9c669aec7358e04b404fbc3ff44d9

Javaid U., Afroz S., Ashraf W., Saghir K.A., Alqahtani F., Anjum S.M.M., Ahmad T., Imran I.

AUTHOR FULL NAMES: Javaid, Usman (57219663243); Afroz, Syeda (12769150800); Ashraf, Waseem (58564789900); Saghir, Khaled Ahmed (57219666704); Alqahtani, Faleh (57199056965); Anjum, Syed Muhammad Muneeb (35110456800); Ahmad, Tanveer (57195283965); Imran, Imran (43861460900)

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Ameliorative effect of Nyctanthes arbor-tristis L. by suppression of pentylenetetrazole-induced kindling in mice: An insight from EEG, neurobehavioral and in-silico studies

(2024) Biomedicine and Pharmacotherapy, 175, art. no. 116791, Cited 2 times.

DOI: 10.1016/j.biopha.2024.116791

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85193618112&doi=10.1016%2fj.biopha.2024.116791&partnerID=40&md5=d51736c8d778b7209262dd390ea29e31

Thakur M., Junho C.V.C., Bernhard S.M., Schindewolf M., Noels H., Döring Y.

AUTHOR FULL NAMES: Thakur, Manovriti (57201339918); Junho, Carolina Victoria Cruz (57218316378); Bernhard, Sarah Maike (57211577925); Schindewolf, Marc (23502374900); Noels, Heidi (17342638800); Döring, Yvonne (22233586100)

57201339918; 57218316378; 57211577925; 23502374900; 17342638800; 22233586100

NETs-Induced Thrombosis Impacts on Cardiovascular and Chronic Kidney Disease

(2023) Circulation Research, 132 (8), pp. 933 - 949, Cited 21 times.

DOI: 10.1161/CIRCRESAHA.123.321750

Vavrincová-Yaghi D. "Indolamine 2,3-dioxygenase - a new approach in the therapy of fibrotic diseases." APVV-23-0399

– Chief researcher

Fibrosis can affect any organ and is ultimately responsible for up to 45% of all deaths. Although each type of organ fibrosis has its own specifics, its basic features are the same. There is activation or proliferation of resident fibroblasts that produce collagen and ECM. In addition, the conversion of epithelial cells of organs into fibroblasts occurs through EMTs, which further contribute to fibrosis. Our published papers and recent preliminary data show that IDO is also involved in fibrosis. IDO metabolizes tryptophan, but it is also involved in several pathologies or plays a protective role in others. The main objective of our project is to comprehensively investigate the role of IDO in the therapy of kidney, liver and heart fibrosis. The individual objectives of the project consist of in vitro and in vivo experiments. In vitro experiments, we plan to investigate the exact mechanisms of action on the main signs of fibroblast activation, EMT of epithelial cells, or involvement of individual profibrotic signaling. The types of cells we plan to use in the in vitro experiments will correspond to the individual organs. We plan to investigate IDO inhibition (1 methyltryptophan – 1-MT, gene KO, or silencing), overexpression of IDO and action of IDO metabolism products (kynurenin, kyn and kynurenic acid, Kyna). In vivo, we will investigate the impact on kidney, liver and heart fibrosis. As a model of liver fibrosis we will use the CCl4 model, the kidney model of unilateral uretra obstruction and the cardiac daunorubicin model. Treatment will consist of administration of 1-MT, or Kyna. Since in our previous publication we have shown, that the IDO 1-MT inhibitor has many non-specific effects, we will also use IDO KO mice to investigate the IDO (non)specific antifibrotic effect of substances. The results of this project could lead to new antifibrotic agents that would help patients with fibrosis, as its therapy is currently very limited or almost non-existent.

Vavrincová D. „Antifibrotic potential of kynurenic acid.“ 1/0513/24

– Chief researcher

Fibrosis is one of the most difficult medical problems to solve. Even though it is a widespread disease that affects almost every organ, there is no effective therapy. The currently available drugs have limited indication and undesirable effects. Kynurenic acid (KYNA) is a metabolite of the enzyme indoleamine 2,3-dioxygenase (IDO). We have been investigating the therapeutic effect of IDO in various diseases for a long time, but recently we have been focusing on its anti-fibrotic potential, which according to our preliminary data may be KYNA. This is in accordance with the latest knowledge. Moreover, KYNA appears to be a completely safe and non-toxic substance. All this makes it a suitable candidate for fibrosis therapy. In the presented project, we therefore plan to investigate the antifibrotic effect of KYNA on several in vitro as well as in vivo fibrotic models. We hope to bring new knowledge to the field of antifibrotic therapy, thus making a small contribution to the solution of this complex problem.

Vavrincová D. „Interference with the indoleamine 2,3-dioxygenase metabolism as a new therapeutic strategy to prevent fibrotic diseases.“ 1/0027/20

– Chief researcher

Almost half of the deaths in the industrialized world are the result of complications related to fibroproliferative diseases. Fibrosis affects every organ, and although some signs of fibrosis vary depending on the affected tissue, the basic features of all fibrotic diseases are the same. Despite the enormous impact of fibrosis on human health, there is still no effective therapy and / or therapeutic approach that interferes with the mechanism of fibrosis. Recently, it has been shown that the enzyme indoleamine 2,3 dioxygenase (IDO) plays a role in fibrosis, which is also consistent with our pre-primary data. IDO is a good candidate for fibrosis therapy because it could affect fibrosis comprehensively, at different levels of its mechanism, as well as in different organs / tissues. In this project, we therefore monitor the impact of several aspects of IDO metabolism on different models of fibrosis in vitro and in vivo, in order to find the optimal strategy for the treatment of fibrotic diseases, as well as to elucidate the hitherto unclear mechanisms of fibrosis at the molecular level.

Vavrinec P. „The role of DNA repair in cellular senescence associated with cardiovascular and renal disease VEGA 1/0121/22

– Scientific co-worker

Aging is associated with the presence of several serious diseases. These diseases include, but are not limited to, cardiovascular and renal disease. Cellular senescence is characterized by irreversible cell cycle arrest and accompanies the aging process. DNA damage is one of the triggers of cellular senescence that occurs when a cell fails to repair damaged DNA. Accumulation of damaged DNA is one of the theories of aging. Methylguanine methyltransferase (MGMT) belongs to a group of enzymes involved in DNA repair. The role of MGMT in senescence has not been investigated so far and our preliminary results show that it can play a significant role here. The present project will be of particular benefit in the area of vascular dysfunction and renal diseases associated with higher age but may also reveal adverse effects of MGMT inhibitors therapy used in cancer therapy. Additionally, this project could lead to the discovery of a new model of senescence, which would be beneficial in research of new treatments.

Vavrinec P. "Intervention in tryptophan metabolism as a therapeutic-diagnostic tool in renal aging in clinical and experimental conditions" VEGA 1/0247/17 – Scientific co-worker