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...
Main Authors: | , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2023-10-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-023-43692-9 |
_version_ | 1797452656398041088 |
---|---|
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. |
first_indexed | 2024-03-09T15:11:48Z |
format | Article |
id | doaj.art-76635020b8374b1fa4ed243074a5e462 |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-03-09T15:11:48Z |
publishDate | 2023-10-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Scientific Reports |
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 |
work_keys_str_mv | AT erikmarkorjan theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT esztersarakormanyos theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT gabriellamihaleknefur theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT agnesdombi theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT emeserekabalint theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT zsoltballa theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT beataadelbalog theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT agnesdago theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT ahmadtotonji theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT zoardistvanbatai theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT eszterpetrajuranyi theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT tamasditroi theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT ammaralomari theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT gaborpozsgai theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT viktoriakormos theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT peternagy theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT erikapinter theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT zoltanrakonczay theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT lorandkiss theantiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT erikmarkorjan antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT esztersarakormanyos antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT gabriellamihaleknefur antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT agnesdombi antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT emeserekabalint antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT zsoltballa antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT beataadelbalog antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT agnesdago antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT ahmadtotonji antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT zoardistvanbatai antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT eszterpetrajuranyi antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT tamasditroi antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT ammaralomari antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT gaborpozsgai antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT viktoriakormos antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT peternagy antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT erikapinter antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT zoltanrakonczay antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis AT lorandkiss antiinflammatoryeffectofdimethyltrisulfideinexperimentalacutepancreatitis |