The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis

Abstract 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 caeru...

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Main Authors: Erik Márk Orján, Eszter Sára Kormányos, Gabriella Mihalekné Fűr, Ágnes Dombi, Emese Réka Bálint, Zsolt Balla, Beáta Adél Balog, Ágnes Dágó, Ahmad Totonji, Zoárd István Bátai, Eszter Petra Jurányi, Tamás Ditrói, Ammar Al-Omari, Gábor Pozsgai, Viktória Kormos, Péter Nagy, Erika Pintér, Zoltán Rakonczay, Lóránd Kiss
Format: Article
Language:English
Published: Nature Portfolio 2023-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-43692-9
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author Erik Márk Orján
Eszter Sára Kormányos
Gabriella Mihalekné Fűr
Ágnes Dombi
Emese Réka Bálint
Zsolt Balla
Beáta Adél Balog
Ágnes Dágó
Ahmad Totonji
Zoárd István Bátai
Eszter Petra Jurányi
Tamás Ditrói
Ammar Al-Omari
Gábor Pozsgai
Viktória Kormos
Péter Nagy
Erika Pintér
Zoltán Rakonczay
Lóránd Kiss
author_facet Erik Márk Orján
Eszter Sára Kormányos
Gabriella Mihalekné Fűr
Ágnes Dombi
Emese Réka Bálint
Zsolt Balla
Beáta Adél Balog
Ágnes Dágó
Ahmad Totonji
Zoárd István Bátai
Eszter Petra Jurányi
Tamás Ditrói
Ammar Al-Omari
Gábor Pozsgai
Viktória Kormos
Péter Nagy
Erika Pintér
Zoltán Rakonczay
Lóránd Kiss
author_sort Erik Márk Orján
collection DOAJ
description Abstract 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 Ca2+ 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 Ca2+ 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.
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spelling doaj.art-76635020b8374b1fa4ed243074a5e4622023-11-26T13:20:04ZengNature PortfolioScientific Reports2045-23222023-10-0113111910.1038/s41598-023-43692-9The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitisErik Márk Orján0Eszter Sára Kormányos1Gabriella Mihalekné Fűr2Ágnes Dombi3Emese Réka Bálint4Zsolt Balla5Beáta Adél Balog6Ágnes Dágó7Ahmad Totonji8Zoárd István Bátai9Eszter Petra Jurányi10Tamás Ditrói11Ammar Al-Omari12Gábor Pozsgai13Viktória Kormos14Péter Nagy15Erika Pintér16Zoltán Rakonczay17Lóránd Kiss18Department of Pathophysiology, University of SzegedDepartment of Pathophysiology, University of SzegedDepartment of Pathophysiology, University of SzegedDepartment of Pharmacology and Pharmacotherapy, Medical School, University of PécsDepartment of Pathophysiology, University of SzegedDepartment of Pathophysiology, University of SzegedDepartment of Pathophysiology, University of SzegedDepartment of Pathophysiology, University of SzegedDepartment of Pathophysiology, University of SzegedDepartment of Pharmacology and Pharmacotherapy, Medical School, University of PécsDepartment of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of OncologyDepartment of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of OncologyDepartment of Pharmacology and Pharmacotherapy, Medical School, University of PécsDepartment of Pharmacology and Pharmacotherapy, Medical School, University of PécsDepartment of Pharmacology and Pharmacotherapy, Medical School, University of PécsDepartment of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of OncologyDepartment of Pharmacology and Pharmacotherapy, Medical School, University of PécsDepartment of Pathophysiology, University of SzegedDepartment of Pathophysiology, University of SzegedAbstract 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 Ca2+ 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 Ca2+ 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.https://doi.org/10.1038/s41598-023-43692-9
spellingShingle Erik Márk Orján
Eszter Sára Kormányos
Gabriella Mihalekné Fűr
Ágnes Dombi
Emese Réka Bálint
Zsolt Balla
Beáta Adél Balog
Ágnes Dágó
Ahmad Totonji
Zoárd István Bátai
Eszter Petra Jurányi
Tamás Ditrói
Ammar Al-Omari
Gábor Pozsgai
Viktória Kormos
Péter Nagy
Erika Pintér
Zoltán Rakonczay
Lóránd Kiss
The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis
Scientific Reports
title The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis
title_full The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis
title_fullStr The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis
title_full_unstemmed The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis
title_short The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis
title_sort anti inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis
url https://doi.org/10.1038/s41598-023-43692-9
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