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

Orján, Erik Márk and Kormányos, Eszter Sára and Mihalekné Fűr, Gabriella and Dombi, Ágnes and Bálint, Emese Réka and Balla, Zsolt and Balog, Beáta Adél and Dágó, Ágnes and Totonji, Ahmad and Bátai, István Zoárd and Jurányi, Eszter Petra and Ditrói, Tamás and Al-omari, Ammar and Pozsgai, Gábor and Kormos, Viktória and Nagy, Péter and Pintér, Erika and Rakonczay, Zoltán and Kiss, Lóránd (2023) The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis. SCIENTIFIC REPORTS, 13 (1). No.-16813. ISSN 2045-2322

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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 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.

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