TY - JOUR AU - Orján, Erik Márk AU - Kormányos, Eszter Sára AU - Fűr, Gabriella AU - Dombi, Ágnes AU - Bálint, Emese Réka AU - Balla, Zsolt AU - Balog, Beáta Adél AU - Dágó, Ágnes AU - Totonji, Ahmad AU - Bátai, István Zoárd AU - Jurányi, Eszter Petra AU - Ditrói, Tamás AU - Al-omari, Ammar AU - Pozsgai, Gábor AU - Kormos, Viktória AU - Nagy, Péter AU - Pintér, Erika AU - Rakonczay, Zoltán AU - Kiss, Lóránd TI - The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 19 SN - 2045-2322 DO - 10.1038/s41598-023-43692-9 UR - https://m2.mtmt.hu/api/publication/34183455 ID - 34183455 N1 - * Megosztott szerzőség AB - Various organosulfur compounds, such as dimethyl trisulfide (DMTS), display anti-inflammatory properties. We aimed to examine the effects of DMTS on acute pancreatitis (AP) and its mechanism of action in both in vivo and in vitro studies. AP was induced in FVB/n mice or Wistar rats by caerulein, ethanol-palmitoleic acid, or L-ornithine-HCl. DMTS treatments were administered subcutaneously. AP severity was assessed by pancreatic histological scoring, pancreatic water content, and myeloperoxidase activity measurements. The behaviour of animals was followed. Pancreatic heat shock protein 72 (HSP72) expression, sulfide, and protein persulfidation were measured. In vitro acinar viability, intracellular Ca 2+ concentration, and reactive oxygen species production were determined. DMTS dose-dependently decreased the severity of AP. It declined the pancreatic infiltration of leukocytes and cellular damage in mice. DMTS upregulated the HSP72 expression during AP and elevated serum sulfide and low molecular weight persulfide levels. DMTS exhibited cytoprotection against hydrogen peroxide and AP-inducing agents. It has antioxidant properties and modulates physiological but not pathophysiological Ca 2+ signalling. Generally, DMTS ameliorated AP severity and protected pancreatic acinar cells. Our findings indicate that DMTS is a sulfur donor with anti-inflammatory and antioxidant effects, and organosulfur compounds require further investigation into this potentially lethal disease. LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Lóránd AU - Fűr, Gabriella AU - Sailaja, Pisipati AU - Prasad, Rajalingamgari AU - Nils, Ewald AU - Vijay, Singh AU - Rakonczay, Zoltán TI - Mechanisms linking hypertriglyceridemia to acute pancreatitis JF - ACTA PHYSIOLOGICA J2 - ACTA PHYSIOL VL - 237 PY - 2023 IS - 3 PG - 21 SN - 1748-1708 DO - 10.1111/apha.13916 UR - https://m2.mtmt.hu/api/publication/33620612 ID - 33620612 N1 - Funding Agency and Grant Number: DOD [PR 191945]; Emberi Eroforrasok Miniszteriuma [EFOP- 3.6.2- 16- 2017- c]; Innovacios es Technologiai Miniszterium [UNKP- 21- 5- SZTE- 577]; Magyar Tudomanyos Akademia [BO/00866/20/5]; European Regional Development Fund [GINOP- 2.3.2- 15- 2016- 00048]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK092460, R01DK119646]; Nemzeti Kutatasi Fejlesztesi es Innovacios Hivatal [K135874, PD129114]; University of Szeged Open Access Fund [6038] Funding text: DOD, Grant/Award Number: PR 191945; Emberi Eroforrasok Miniszteriuma, Grant/Award Number: EFOP- 3.6.2- 16- 2017- 00006; Innovacios es Technologiai Miniszterium, Grant/Award Number: UNKP- 21- 5- SZTE- 577; Magyar Tudomanyos Akademia, Grant/Award Number: BO/00866/20/5; European Regional Development Fund, Grant/Award Number: GINOP- 2.3.2- 15- 2016- 00048; National Institute of Diabetes and Digestive and Kidney Diseases, Grant/Award Number: R01DK092460 and R01DK119646; Nemzeti Kutatasi Fejlesztesi es Innovacios Hivatal, Grant/Award Number: K135874 and PD129114; University of Szeged Open Access Fund, Grant/Award Number: 6038 AB - Hypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important etiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG-induced AP and the clinically observed effects of HTG on the outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG-induced AP or AP in the presence of HTG and determining possible treatments are needed. LA - English DB - MTMT ER - TY - JOUR AU - Bálint, Emese Réka AU - Fűr, Gabriella AU - Kui, Balázs AU - Balla, Zsolt AU - Kormányos, Eszter Sára AU - Orján, Erik Márk AU - Tóth, Brigitta AU - Horváth, Gyöngyi AU - Szűcs, Edina AU - Benyhe, Sándor AU - Ducza, Eszter AU - Pallagi, Petra AU - Maléth, József AU - Venglovecz, Viktória AU - Hegyi, Péter AU - Kiss, Lóránd AU - Rakonczay, Zoltán TI - Fentanyl but Not Morphine or Buprenorphine Improves the Severity of Necrotizing Acute Pancreatitis in Rats JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 3 PG - 23 SN - 1661-6596 DO - 10.3390/ijms23031192 UR - https://m2.mtmt.hu/api/publication/32624010 ID - 32624010 N1 - Department of Pathophysiology, University of Szeged, Szeged, 6725, Hungary Department of Medicine, University of Szeged, Szeged, 6725, Hungary Department of Physiology, University of Szeged, Szeged, 6725, Hungary Institute of Biochemistry, Biological Research Center, Szeged, 6726, Hungary Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, 6725, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, 6725, Hungary Institute for Translational Medicine, Medical School, University of Pecs, Pecs, 7624, Hungary Cited By :4 Export Date: 16 October 2023 Correspondence Address: Kiss, L.; Department of Pathophysiology, Hungary; email: lorand.kiss.work@gmail.com Correspondence Address: Rakonczay, Z.; Department of Pathophysiology, Hungary; email: rakonczay.zoltan@med.u-szeged.hu Chemicals/CAS: amylase, 9000-90-2, 9000-92-4, 9001-19-8; buprenorphine, 52485-79-7, 53152-21-9; ceruletide, 17650-98-5; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine], 78123-71-4; fentanyl, 437-38-7, 1443-54-5; gentamicin, 1392-48-9, 1403-66-3, 1405-41-0; ketamine, 1867-66-9, 6740-88-1, 81771-21-3; morphine, 52-26-6, 57-27-2; myeloperoxidase; naloxone, 357-08-4, 465-65-6; ornithine, 70-26-8, 7006-33-9; taurocholic acid, 145-42-6, 59005-70-8, 81-24-3; xylazine, 23076-35-9, 7361-61-7; Analgesics, Opioid; Buprenorphine; Fentanyl; Morphine; Receptors, Opioid, mu Tradenames: PE-10, Becton Dickinson, United States; PE-10, Clay Adams, United States Manufacturers: CP Pharmaceuticals, Germany; Sigma Aldrich, HungaryBecton Dickinson, United States; Clay Adams, United States Funding text 1: Funding: This work was supported by EFOP-3.6.2–16–2017–00006, GINOP-2.3.2-15-2016-00048, Bólyai János Research Grant (BO/00866/20/5), ÚNKP Grant (ÚNKP-20-5-SZTE-163), NKFIH PD129114 and NKFIH K119938. The funders did not influence the interpretation of results in any way. AB - Opioids are widely used for the pain management of acute pancreatitis (AP), but their impact on disease progression is unclear. Therefore, our aim was to study the effects of clinically relevant opioids on the severity of experimental AP. Various doses of fentanyl, morphine, or buprenorphine were administered as pre- and/or post-treatments in rats. Necrotizing AP was induced by the intraperitoneal injection of L-ornithine-HCl or intra-ductal injection of Na-taurocholate, while intraperitoneal caerulein administration caused edematous AP. Disease severity was determined by laboratory and histological measurements. Mu opioid receptor (MOR) expression and function was assessed in control and AP animals. MOR was expressed in both the pancreas and brain. The pancreatic expression and function of MOR were reduced in AP. Fentanyl post-treatment reduced necrotizing AP severity, whereas pre-treatment exacerbated it. Fentanyl did not affect the outcome of edematous AP. Morphine decreased vacuolization in edematous AP, while buprenorphine pre-treatment increased pancreatic edema during AP. The overall effects of morphine on disease severity were negligible. In conclusion, the type, dosing, administration route, and timing of opioid treatment can influence the effects of opioids on AP severity. Fentanyl post-treatment proved to be beneficial in AP. Clinical studies are needed to determine which opioids are best in AP. LA - English DB - MTMT ER - TY - JOUR AU - Fűr, Gabriella AU - Kiss, Lóránd AU - Bálint, Emese Réka AU - Kormányos, Eszter Sára AU - Balla, Zsolt AU - Czira, B AU - Venglovecz, Viktória AU - Pallagi, Petra AU - Maléth, József AU - Hegyi, Péter AU - Rakonczay, Zoltán TI - The CFTR corrector vx-661 as a therapeutic option in experimental acute pancreatitis JF - CENTRAL EUROPEAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY / GASZTROENTEROLÓGIAI ÉS HEPATOLÓGIAI SZEMLE J2 - CENT EUR J GASTRO HEPATOL VL - 7 PY - 2021 IS - Suppl. 2 SP - 39 EP - 39 PG - 1 SN - 2415-9107 UR - https://m2.mtmt.hu/api/publication/32589482 ID - 32589482 LA - English DB - MTMT ER - TY - JOUR AU - Balla, Zsolt AU - Kormányos, Eszter Sára AU - Kui, Balázs AU - Bálint, Emese Réka AU - Fűr, Gabriella AU - Orján, Erik Márk AU - Iványi, Béla AU - Vécsei, László AU - Fülöp, Ferenc AU - Varga, Gabriella AU - Harazin, András AU - Tubak, Vilmos AU - Deli, Mária Anna AU - Papp, Csaba Gergő AU - Gácser, Attila AU - Madácsy, Tamara AU - Venglovecz, Viktória AU - Maléth, József AU - Hegyi, Péter AU - Kiss, Lóránd AU - Rakonczay, Zoltán TI - Kynurenic acid and its analogue SZR-72 ameliorate the severity of experimental acute necrotizing pancreatitis JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 12 PY - 2021 PG - 15 SN - 1664-3224 DO - 10.3389/fimmu.2021.702764 UR - https://m2.mtmt.hu/api/publication/32258744 ID - 32258744 LA - English DB - MTMT ER - TY - JOUR AU - Fűr, Gabriella AU - Bálint, Emese Réka AU - Orján, Erik Márk AU - Balla, Zsolt AU - Kormányos, Eszter Sára AU - Czira, Beáta AU - Szűcs, Attila AU - Kovács, Dénes Péter AU - Pallagi, Petra AU - Maléth, József AU - Venglovecz, Viktória AU - Hegyi, Péter AU - Kiss, Lóránd AU - Rakonczay, Zoltán TI - Mislocalization of CFTR expression in acute pancreatitis and the beneficial effect of VX-661 + VX-770 treatment on disease severity JF - JOURNAL OF PHYSIOLOGY-LONDON J2 - J PHYSIOL-LONDON VL - 599 PY - 2021 IS - 22 SP - 4955 EP - 4971 PG - 17 SN - 0022-3751 DO - 10.1113/JP281765 UR - https://m2.mtmt.hu/api/publication/32256056 ID - 32256056 N1 - * Megosztott szerzőség AB - Cystic fibrosis transmembrane conductance regulator (CFTR) is an important ion channel in epithelial cells. Its malfunction has several serious consequences, like developing or aggravating acute pancreatitis (AP). Here, we investigated the localization and expression of CFTR during cerulein-induced AP in mice and determined the effects of CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. CFTR mRNA expression was significantly increased, and mislocalization of CFTR protein was observed in AP compared to the control group. Interestingly, pre-treatment of AP mice with VX-661 + VX-770 significantly reduced the extent of pancreatic tissue damage by 20-30%. In vitro administration of VX-661 + VX-770 significantly increased the fluid secretion of ducts derived from AP animals. Based on our results, the utilization of CFTR correctors and potentiators should be further investigated in AP.Cystic fibrosis transmembrane conductance regulator (CFTR) has essential role in maintaining pancreatic ductal function. Impaired CFTR function can trigger acute pancreatitis (AP) and exacerbate disease severity. We aimed to investigate the localization and expression of CFTR during AP, and determined the effects of CFTR corrector (VX-661) and potentiator (VX-770) on disease severity. AP was induced in FVB/n mice by 6-10 hourly intraperitoneal injections of 50μg/kg cerulein. Some mice were pre-treated with 5-6 daily injections of 2mg/kg VX-661+VX-770. Control animals were administered physiological saline instead of cerulein and DMSO instead of VX compounds. AP severity was determined by measuring laboratory and histological parameters; CFTR and CK19 expressions were measured. Activity of ion transporters was followed by intracellular pH or fluid secretion measurement of isolated pancreatic intra-/interlobular ducts. Cerulein-induced AP severity was greatest between 12-24h. CFTR mRNA expression was significantly increased 24h after AP induction. Immunohistochemistry demonstrated disturbed staining morphology of CFTR and CK19 proteins in AP. Mislocalization of CFTR protein was observed from 6h, while expression increased at 24h compared to control. Ductal HCO3- transport activity was significantly increased 6h after AP induction. AP mice pre-treatment with VX-661+VX-770 significantly reduced the extent of tissue damage by about 20-30%, but other parameters were unchanged. Interestingly, VX-661+VX-770 in vitro administration significantly increased the fluid secretion of ducts derived from AP animals. This study described the course of the CFTR expression and mislocalization in cerulein-induced AP. Our results suggest that the beneficial effects of CFTR correctors and potentiators should be further investigated in AP. This article is protected by copyright. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Kormányos, Eszter Sára AU - Balla, Zsolt AU - Fűr, Gabriella AU - Bálint, Emese Réka AU - Totonji, A. AU - Bátai, Z. AU - Pozsgai, G. AU - Börzsönyi, I AU - Hegyi, P. AU - Pintér, E. AU - Rakonczay, Zoltán AU - Kiss, Lóránd TI - Investigation of dimethyl trisulfide as a promising therapeutic agent in experimental acute pancreatitis JF - PANCREATOLOGY J2 - PANCREATOLOGY VL - 20 PY - 2020 IS - Suppl 1 SP - S60 EP - S61 PG - 2 SN - 1424-3903 DO - 10.1016/j.pan.2020.07.078 UR - https://m2.mtmt.hu/api/publication/31722663 ID - 31722663 LA - English DB - MTMT ER - TY - JOUR AU - Fűr, Gabriella AU - Kiss, Lóránd AU - Bálint, Emese Réka AU - Kormányos, Eszter Sára AU - Balla, Zsolt AU - Czira, B. AU - Venglovecz, V. AU - Pallagi, Petra AU - Maléth, József AU - Hegyi, P. AU - Rakonczay, Zoltán TI - The beneficial effect of the CFTR corrector VX-661 in experimental acute pancreatitis JF - PANCREATOLOGY J2 - PANCREATOLOGY VL - 20 PY - 2020 IS - Suppl 1 SP - S61 EP - S61 PG - 1 SN - 1424-3903 DO - 10.1016/j.pan.2020.07.079 UR - https://m2.mtmt.hu/api/publication/31722531 ID - 31722531 LA - English DB - MTMT ER - TY - JOUR AU - Bálint, Emese Réka AU - Balla, Zsolt AU - Kui, Balázs AU - Kiss, Lóránd AU - Fűr, Gabriella AU - Kormányos, Eszter Sára AU - Pallagi, Petra AU - Venglovecz, Viktória AU - Maléth, József AU - Hegyi, Péter AU - Rakonczay, Zoltán TI - Fentanyl ameliorates the severity of necrotizing, but not edematous acute pancreatitis in rats JF - PANCREATOLOGY J2 - PANCREATOLOGY VL - 20 PY - 2020 IS - Suppl 1 SP - S59 EP - S60 PG - 2 SN - 1424-3903 DO - 10.1016/j.pan.2020.07.076 UR - https://m2.mtmt.hu/api/publication/31722419 ID - 31722419 LA - English DB - MTMT ER - TY - BOOK ED - Kiss, Lóránd ED - Rakonczay, Zoltán TI - EFOP-3.6.2-16-2017-00006 konzorciális pályázat megvalósulásának bemutatása PB - Szegedi Tudományegyetem (SZTE) CY - Szeged PY - 2020 SP - 88 SN - 9789633067680 UR - https://m2.mtmt.hu/api/publication/31673830 ID - 31673830 LA - Hungarian DB - MTMT ER -