https://m2.mtmt.hu/ hun 2026-09-21 16:49 JournalArticle 30857506 VALIDATED true 0 false 2026-09-21T09:41:07.399+0000 2026-02-09T10:10:41.133+0000 2019-10-22T10:39:45.526+0000 true 10039043 Milánkovics Róbert /api/admin/10039043 Admin true 10039043 2026-07-29T08:36:22.165+0000 2024-11-28T05:53:07.115+0000 true 10039043 Milánkovics Róbert /api/admin/10039043 Admin true 10039043 Admin 10003134 /api/admin/10003134 Wolf György true 10003134 true 2026-02-03T09:39:04.200+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Tóth, Emese Novel mitochondrial transition pore inhibitor N-methyl-4-isoleucine cyclosporin is a new therapeutic option in acute pancreatitis true true /api/journal/1000011 REVIEWED true false 1000011 false 1000011 true 0022-3751 1469-7793 Journal FOREIGN 597 24 5879 5898 5879 20 2019 •Bile acids, ethanol and fatty acids deteriorate pancreatic ductal fluid and bicarbonate secretion via mitochondrial damage, ATP depletion and calcium overload. •It is known that pancreatitis inducing factors open the membrane transition pore (mPTP) channel via cyclophilin D activation in acinar cells causing calcium overload and cell death and genetic or pharmacological inhibition of mPTP improves the outcome of acute pancreatitis in animal models. •In our study we show that genetic and pharmacological inhibition of mPTP protects mitochondrial homeostasis and cell function evoked by pancreatitis-inducing factors in pancreatic ductal cells. •Our results also reveal that the novel Cyclosporin A derivative NIM811 protects mitochondrial function in acinar and ductal cells, moreover it preserves bicarbonate transport mechanisms in pancreatic ductal cells. •We found that NIM811 is highly effective in different experimental pancreatitis models and that NIM811 has no side-effects. NIM811 is a highly suitable compound to be tested in clinical trials .Background and aims Mitochondrial dysfunction plays a crucial role in the development of acute pancreatitis (AP); however, no compound is currently available with clinically acceptable effectiveness and safety. In this study, we investigated the effects of a novel mitochondrial transition pore inhibitor, N-methyl-4-isoleucine cyclosporin (NIM811), in AP. Methods Pancreatic ductal and acinar cells were isolated by enzymatic digestion from Bl/6 mice. In vitro measurements were performed by confocal microscopy and microfluorometry. Preventive effects of pharmacological (cylosporin A (2 µM), NIM811 (2 µM)) or genetic (Ppif-/- /Cyp D KO) inhibition of the mitochondrial transition pore (mPTP) during the administration of either bile acids (BA) or ethanol + fatty acids (EtOH+FA) were examined. Toxicity of mPTP inhibition was investigated by detecting apoptosis and necrosis. In vivo effects of the most promising compound, NIM811 (5 or 10 mg/kg per os), were checked in three different AP models induced by either caerulein (10 × 50 µg/kg), ethanol+ fatty acid (1.75 g/kg ethanol and 750 mg/kg palmitic acid) or 4% taurocholic acid (2 ml/kg). Results Both genetic and pharmacological inhibition of Cyp D significantly prevented the toxic effects of BA and EtOH+FA by restoring mitochondrial membrane potential (Δψ) and preventing the loss of mitochondrial mass. In vivo experiments revealed that per os administration of NIM811 has a protective effect in AP by reducing oedema, necrosis, leukocyte infiltration and serum amylase level in AP models. Administration of NIM811 had no toxic effects. Conclusion The novel mitochondrial transition pore inhibitor NIM811 seems to be an exceptionally good candidate compound for clinical trials in AP. This article is protected by copyright. All rights reserved. Funding 1997177 /api/funding/1997177 false true Funding 2015380 /api/funding/2015380 false true true 2019 true true true false true false GOLD 2026-09-21 true https://doi.org/10.1113/JP278517 45 0 43 37 6 45 43 36 40 41 41 35 35 39 6 0 45 39 43 37 0 19 19 Folyóiratcikk Journal Article 24 41 Könyvrészlet Chapter in Book 25 2 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 2 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2019 0 1 1 1 1 2020 0 6 5 6 5 2021 0 8 7 8 7 2022 0 2 1 2 1 2023 0 6 5 6 5 2024 0 7 6 7 6 2025 0 9 8 9 8 2026 0 6 6 6 6 D1 false 10015508,10000098 false false false 2019-12-12T10:03:31.010+0000 Farmakológiai és Farmakoterápiai Intézet (SZTE / SZAOK); I. sz. Belgyógyászati Klinika (PTE / ÁOK); I. sz. Belgyógyászati Klinika (SZTE / SZAOK / BK); Kórélettani Intézet (SZTE / SZAOK); MTA-SZTE Lendület Epitél Sejt Szignalizáció és ... (SZTE / SZAOK / BK); MTA-SZTE Lendület Gasztroenterológiai Multidisz... (SZTE / SZAOK / BK / I.BelK); Orvosi Biokémiai Intézet (SE / AOK / I); Transzlációs Medicina Intézet (PTE / ÁOK); Transzlációs medicina kutatócsoport (PTE / SZKK) 10 45 9 13 0 true 10003134 Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 88294943 /api/authorship/88294943 1 0.077 true false false Author 10054987 /api/author/10054987 Tóth Emese true 10054987 true Tóth Emese true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294944 /api/authorship/88294944 2 0.07692308 false false false Author 10030084 /api/author/10030084 Maléth József true 10030084 true Maléth József true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294945 /api/authorship/88294945 3 0.07692308 false false false Závogyán Noémi true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294946 /api/authorship/88294946 4 0.077 false false false Author 10054985 /api/author/10054985 Fanczal Júlia true 10054985 true Fanczal Júlia true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294947 /api/authorship/88294947 5 0.07692308 false false false Grassalkovich Anna true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294948 /api/authorship/88294948 6 0.07692308 false false false Erdős Réka true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294949 /api/authorship/88294949 7 0.077 false false false Author 10030075 /api/author/10030075 Pallagi Petra true 10030075 true Pallagi Petra true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294950 /api/authorship/88294950 8 0.07692308 false false false Author 10046147 /api/author/10046147 Horváth Gergő true 10046147 true Horváth Gergő true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294951 /api/authorship/88294951 9 0.07692308 false false false Author 10015508 /api/author/10015508 Tretter László true 10015508 true Tretter László true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294952 /api/authorship/88294952 10 0.07692308 false false false Author 10055000 /api/author/10055000 Bálint Emese Réka true 10055000 true Bálint Emese Réka true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294953 /api/authorship/88294953 11 0.07692308 false false false Author 10000098 /api/author/10000098 Rakonczay Zoltán true 10000098 true Rakonczay Zoltán true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88294954 /api/authorship/88294954 12 0.07692308 false false false Author 10022556 /api/author/10022556 Venglovecz Viktória true 10022556 true Venglovecz Viktória true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 88296858 /api/authorship/88296858 13 0.07692308 false true true Author 10002629 /api/author/10002629 Hegyi Péter true 10002629 true Hegyi Péter true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PublicationIdentifier 15994829 /api/publicationidentifier/15994829 PlainSource 6 /api/publicationsource/6 PublicationSourceType 10001 /api/publicationsourcetype/10001 true true true DOI DOI https://doi.org/@@@ true true 6 true GOLD true IDENTICAL 10.1113/JP278517 https://doi.org/10.1113/JP278517 false true PublicationIdentifier 17872852 /api/publicationidentifier/17872852 PlainSource 1 /api/publicationsource/1 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true WoS WoS https://www.webofscience.com/wos/woscc/full-record/@@@ true true 1 true IDENTICAL 000578238700017 https://www.webofscience.com/wos/woscc/full-record/000578238700017 false true PublicationIdentifier 16213953 /api/publicationidentifier/16213953 PlainSource 3 /api/publicationsource/3 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true Scopus Scopus http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@ true true 3 true IDENTICAL 85075798185 http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85075798185 false true PublicationIdentifier 15994828 /api/publicationidentifier/15994828 PlainSource 17 /api/publicationsource/17 PublicationSourceType 10003 /api/publicationsourcetype/10003 false true true PubMed PubMed http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract true true 17 true IDENTICAL 31631343 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=31631343&dopt=Abstract false true PublicationIdentifier 16536972 /api/publicationidentifier/16536972 SwordSource 90 /api/publicationsource/90 PublicationSourceType 10007 /api/publicationsourcetype/10007 true true true SZTE Publicatio SZTE Publicatio http://publicatio.bibl.u-szeged.hu/@@@ true true 90 true GREEN true DIFFERENT 17959 http://publicatio.bibl.u-szeged.hu/17959 false true Classification 12125 /api/classification/12125 true true Classification 10554 /api/classification/10554 true true Classification 10575 /api/classification/10575 true true Classification 12184 /api/classification/12184 true true Keyword 1011239 /api/keyword/1011239 true 1011239 true Keyword 1517580 /api/keyword/1517580 true true Keyword 1598304 /api/keyword/1598304 true true Keyword 1787492 /api/keyword/1787492 true true SjrRating 10901289 /api/sjrrating/10901289 10 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr true true ClassificationExternal 3699 /api/classificationexternal/3699 true 3699 true D1 DIRECT true true /api/publication/30857506 <div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10054987"><a href="/gui2/?type=authors&mode=browse&sel=10054987" target="_blank">Tóth Emese (<span class="authorship-author-name">Tóth Emese</span> <span class="authorAux-mtmt"> Pancreas experimental Pancreatitis Pancreatology</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Gasztroenterológiai Multidiszciplináris Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10030084"><a href="/gui2/?type=authors&mode=browse&sel=10030084" target="_blank">Maléth József (<span class="authorship-author-name">Maléth József</span> <span class="authorAux-mtmt"> Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Závogyán Noémi </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10054985"><a href="/gui2/?type=authors&mode=browse&sel=10054985" target="_blank">Fanczal Júlia (<span class="authorship-author-name">Fanczal Júlia</span> <span class="authorAux-mtmt"> pancreatitis (alapkutatás)</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Grassalkovich Anna </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Erdős Réka </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10030075"><a href="/gui2/?type=authors&mode=browse&sel=10030075" target="_blank">Pallagi Petra (<span class="authorship-author-name">Pallagi Petra</span> <span class="authorAux-mtmt"> Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Epitél Sejt Szignalizáció és Szekréció Kutatócsoport</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10046147"><a href="/gui2/?type=authors&mode=browse&sel=10046147" target="_blank">Horváth Gergő (<span class="authorship-author-name">Horváth Gergő</span> <span class="authorAux-mtmt"> biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Orvosi Biokémiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10015508"><a href="/gui2/?type=authors&mode=browse&sel=10015508" target="_blank">Tretter László (<span class="authorship-author-name">Tretter László</span> <span class="authorAux-mtmt"> Biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Orvosi Biokémiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10055000"><a href="/gui2/?type=authors&mode=browse&sel=10055000" target="_blank">Bálint Emese Réka (<span class="authorship-author-name">Bálint Emese Réka</span> <span class="authorAux-mtmt"> Pankreatológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Kórélettani Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000098"><a href="/gui2/?type=authors&mode=browse&sel=10000098" target="_blank">Rakonczay Zoltán (<span class="authorship-author-name">Rakonczay Zoltán</span> <span class="authorAux-mtmt"> Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Kórélettani Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10022556"><a href="/gui2/?type=authors&mode=browse&sel=10022556" target="_blank">Venglovecz Viktória (<span class="authorship-author-name">Venglovecz Viktória</span> <span class="authorAux-mtmt"> Pankreász</span>) </a> </span> <span class="author-affil"><span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Farmakológiai és Farmakoterápiai Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10002629"><a href="/gui2/?type=authors&mode=browse&sel=10002629" target="_blank">Hegyi Péter ✉ (<span class="authorship-author-name">Hegyi Péter</span> <span class="authorAux-mtmt"> Gasztroenterológia</span>) </a> </span> <span class="author-affil"><span title="Pécsi Tudományegyetem">PTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/I. sz. Belgyógyászati Klinika; <span title="Szegedi Tudományegyetem">SZTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/<span title="I. sz. Belgyógyászati Klinika">I.BelK</span>/MTA-SZTE Lendület Gasztroenterológiai Multidiszciplináris Kutatócsoport; <span title="Pécsi Tudományegyetem">PTE</span>/<span title="Általános Orvostudományi Kar">ÁOK</span>/Transzlációs Medicina Intézet; <span title="Pécsi Tudományegyetem">PTE</span>/<span title="Szentágothai János Kutatóközpont">SZKK</span>/Transzlációs medicina kutatócsoport</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;30857506" target="_blank">Novel mitochondrial transition pore inhibitor N-methyl-4-isoleucine cyclosporin is a new therapeutic option in acute pancreatitis</a></div> <div> <span class="journal-title">JOURNAL OF PHYSIOLOGY-LONDON</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0022-3751">0022-3751</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1469-7793">1469-7793</a>)</span>: <span class="journal-volume">597</span> <span class="journal-issue">24</span> <span class="page"> pp 5879-5898 </span> <span class="year">(2019)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1113/JP278517" target="_blank" href="https://doi.org/10.1113/JP278517"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000578238700017" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000578238700017"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85075798185" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85075798185"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="31631343" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=31631343&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_GREEN" title=" Green "> <a style="color:blue" title="17959" target="_blank" href="http://publicatio.bibl.u-szeged.hu/17959"> SZTE Publicatio </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Sports Science&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Physiology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 45</span> | Független: 39 | Függő: 6 | Nem jelölt: 0 | WoS jelölt: 36 | Scopus jelölt:&nbsp;40 | WoS/Scopus jelölt:&nbsp;41 | DOI jelölt:&nbsp;43 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;30857506&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 19 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 30857506</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">PubMed (pubmed_result.xml, 2019-10-22)</span> </div> <div class="funder"> EMBERI ERŐFORRÁS FEJLESZTÉSI OPERATÍV PROGRAM (EFOP)(EFOP-3.6.2-162017-00006) Támogató: NKFIH, (GINOP-2.3.2-15-2016-00015) Támogató: GINOP </div> <div class="lastModified">Utolsó módosítás: 2026.02.09. 11:10 Balázs András (MTMT Központ, admin) </div> <div class="lockedBy">Központi kezelésű 2026.02.03. 10:39 Wolf György (MTMT Központi admin) </div> </div></div>