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The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis
Erik Márk Orján1, Eszter Sára Kormányos1, Gabriella Mihalekné Fűr1
1Department of Pathophysiology, University of Szeged, Semmelweis U. 1, 6725, Szeged, Hungary.
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.
Insights
Dimethyl trisulfide (DMTS) reduces acute pancreatitis (AP) severity by decreasing inflammation and cellular damage. This organosulfur compound offers antioxidant effects and protects pancreatic cells, warranting further research for treating this lethal disease.
Area of Science:
- Biochemistry
- Pharmacology
- Gastroenterology
Background:
- Organosulfur compounds, like dimethyl trisulfide (DMTS), possess known anti-inflammatory properties.
- Acute pancreatitis (AP) is a severe inflammatory condition with significant morbidity and mortality.
- Understanding novel therapeutic agents for AP is crucial.
Purpose of the Study:
- To investigate the therapeutic effects of DMTS on acute pancreatitis (AP) in vivo and in vitro.
- To elucidate the underlying mechanisms of DMTS action in AP, including its anti-inflammatory and antioxidant properties.
Main Methods:
- AP was induced in rodents using various methods (caerulein, ethanol-palmitoleic acid, L-ornithine-HCl).
- DMTS treatment efficacy was assessed via histological scoring, myeloperoxidase activity, and animal behavior.
- In vitro studies evaluated acinar cell viability, calcium signaling, and reactive oxygen species production.
Main Results:
- DMTS dose-dependently reduced AP severity, decreasing leukocyte infiltration and pancreatic damage.
- DMTS upregulated heat shock protein 72 (HSP72) expression and increased serum sulfide and persulfide levels.
- DMTS demonstrated cytoprotective effects against oxidative stress and AP-inducing agents, with antioxidant properties.
Conclusions:
- DMTS ameliorates AP severity and protects pancreatic acinar cells through anti-inflammatory and antioxidant mechanisms.
- DMTS acts as a sulfur donor, modulating cellular responses during pancreatitis.
- Organosulfur compounds represent a promising area for further investigation in AP treatment.
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