Protective Effect of Methylsulfonylmethane in Caerulein-Induced Acute Pancreatitis and Associated Lung Injury in Mice

J Pharm Pharmacol. 2018 Sep;70(9):1188-1199. doi: 10.1111/jphp.12946. Epub 2018 Jul 3.

Abstract

Objectives: In the present study, we have elaborated the anti-inflammatory mechanism of MSM through homing of CD34+ stem cells towards an inflamed region by regulating hydrogen sulfide (H2 S) in an in vivo model of caerulein-induced acute pancreatitis (AP) and associated lung injury.

Methods: Male Swiss mice were treated with hourly intraperitoneal injections of caerulein (50 μg/kg) for 6 h. MSM (500 mg/kg) was administered intraperitoneally 1 h after the first caerulein injection (therapeutic). The serum amylase activity and myeloperoxidase (MPO) activity in lung and pancreas were measured. The levels of H2 S and interleukin (IL)-1β, cystathionine-γ-lyase (CSE) and CD34+ expressions in pancreas and lungs were determined by RT-PCR and ELISA.

Key findings: Methylsulfonylmethane significantly ameliorated pancreas and lung histopathological changes, decreased serum amylase, MPO activity and inhibited caerulein-induced IL-1β expression. Furthermore, MSM reduced caerulein-induced H2 S levels by alleviating the expression of CSE in pancreas and lungs and increased CD34 expression and inhibited nuclear factor (NF)-κB translocation in caerulein-induced AP and associated lung injury.

Conclusions: These findings indicate that MSM can effectively reduce inflammatory responses and induce the homing of CD34+ cells to the injured tissues.

Keywords: CD34; acute pancreatitis; hydrogen sulfide; lung injury; methylsulfonylmethane.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / prevention & control*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Ceruletide / toxicity*
  • Dimethyl Sulfoxide / pharmacology
  • Dimethyl Sulfoxide / therapeutic use*
  • Dose-Response Relationship, Drug
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Pancreatitis / chemically induced
  • Pancreatitis / metabolism
  • Pancreatitis / prevention & control*
  • Random Allocation
  • Sulfones / pharmacology
  • Sulfones / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Sulfones
  • Ceruletide
  • dimethyl sulfone
  • Dimethyl Sulfoxide